December 2010, Vol 3, No 8

The addition of new biomarkers forestablishing a prognosis for pa -tients with breast cancer has been

recommended in the 2010 edition of theAmerican Joint Committee of Cancer’sCancer Staging Handbook.1 Human epider-mal growth factor receptor type 2(HER2) status and multigene signature“scores” have been added to estrogenreceptor (ER) and progesterone receptor(PR) determinations.1 So, where are weregarding multigene signature scores? Atthis time, two tests are commercially

available in the United States: OncotypeDX (Genomic Health) and MammaPrint(Agendia).

21-gene recurrence score assayAvailable since 2004, Oncotype DX

uses a process called reverse-transcriptasepolymerase chain reaction (RT-PCR) tolook at 21 genes: 16 are linked to breastcancer and five are reference genes usedfor normalizing the expression of the can-cer-related genes. The chosen genes have

DECEMBER 2010 www.TheOncologyNurse.com VOL 3, NO 8

Journal ofOncology Navigation &Survivorship™

between pages 34 and 35

Journal of Oncology ™

The Official Journal of the Academy of Oncology Nurse Navigators

NAVIGATION & SURVIVORSHIP®

DECEMBER 2010 www.AONNonline.org VOL 1, NO 7

Lillie Shockney, RN, BS, MASJohns Hopkins Breast CenterJohns Hopkins UniversitySchool of MedicineBaltimore, Maryland

Sharon Gentry, RN, MSN, AOCN,CBCNDerrick L. Davis ForsythRegional Cancer CenterWinston-Salem, North Carolina

Nicole Messier, RNVermont Cancer CenterBurlington, Vermont

Pamela Matten, RN, BSN, OCNSt. Joseph HospitalOrange, California

Elaine Sein, RN, BSN, OCN, CBCNFox Chase Cancer Center PartnersRockledge, Pennsylvania

Tricia Strusowski, MS, RNHelen F. Graham Cancer CenterChristiana Care Health SystemNewark, Delaware

Linda Fleisher, MPH, PhD(c)Fox Chase Cancer CenterCheltenham, Pennsylvania

Susan M. Gardner, RN, CBEC, CBCNValley Medical CenterRenton, Washington

Jay R. Swanson, RN, BSN, OCNSaint Elizabeth Cancer InstituteLincoln, Nebraska

Carol Lewis, RN, BSN, OCN, CRNIMemorial HermannThe Woodlands, Texas

Sean T. WalshExecutive [email protected]

Leadership Council

©2010 Green Hill Healthcare Communications, LLC

AONN Staff

www.AONNonline.org

GUIDE OUR PATHStart a Local, State, or Regional Affiliate,

Join a Committee

The George Washington CancerInstitute (GWCI) recently re -ceived a $2.4 million grant from

the DC Cancer Consortium to estab-lish and coordinate a City-wide PatientNavi gation Network (CPNN) inWash ington, DC. The CPNN will create a seamless,

cohesive framework for coordination ofcancer care throughout the city to ensurethat all city residents get appropriate can-cer screening and treatment regardless oftheir ability to pay. The network will alsohelp patients identify support servicesthroughout the cancer continuum, in -cluding posttreatment survivorship. Twenty-five separate institutions,

including hospitals, cancer centers, andcommunity organizations in theWashington, DC, area are members of

the network, and patient navigators areembedded at every site, said StevenPatierno, PhD, executive director ofthe GWCI.

The program, he explained, providestraining once a month to every navigatorand every navigator’s supervisor. It alsoprovides a central communications portal

and a secure Internet-based data collec-tion process, which allows the navigatorsto upload their navigation logs and theirpatient interactions in real time.

He gave an example of how coordina-tion of care works. “If a patient is seen ata community advocacy group that does

Continued on page 2

CARE COORDINATION

City-wide Patient Navigation NetworkCoordinates Washington, DC, Cancer CareBy Karen Rosenberg

The Center for the Advancementof Cancer Survivorship, Navi -gation, and Policy (caSNP), a

collaboration of the George Wash ingtonCancer Institute (GWCI) and the uni-versity’s School of Public Health andHealth Services Department of HealthPolicy, was established in 2009 with support from Pfizer and the PfizerFoundation. The center’s goals are toadvance patient navigation and cancersurvivorship efforts both locally andnationally through training, research,

policy analysis, and education. caSNP grew out of the understanding

that there is “overlap between patientnavigation, survivorship, and policy andboth of these intersect with local andnational healthcare policy,” explainedSteven Patierno, PhD, executive directorof the GWCI. “We wanted to create aplatform to talk about navigation and sur-vivorship in the context of policy in aunited program.” The center offers training programs at

three levels:

• Navigation training is designed fornavigators, including nurses, socialworkers, and lay persons. Traineesfrom institutions across the coun-try learn about barriers that affecttheir patients, are trained tolaunch or improve programs, andgain tools for implementing insti-tutional change.

• Executive level training is de signedfor chief executive officers, chieffinancial officers, hospital adminis-

NAVIGATION TRAINING

Center Provides Platform for Discussion ofCancer Survivorship, Navigation, and Policy By Karen Rosenberg

Continued on page 2

“The CPNN will create a seamless,cohesive framework for coordination ofcancer care throughout the city. ”

—Steven Patierno, PhD

GENETIC TESTING

Multigene Signature Scores andBreast Cancer 2010By Deena Damsky Dell, MSN, RN-BC, AOCN Clinical Nurse Specialist, Fox Chase Cancer Center,Philadelphia


Continued on page 12

Mammography technologist Jessica Davis, RT(R) (M), is part of a multi-disciplinary breast cancer care team working to improve access toscreening, treatment, and research.

Geisinger Medical Center’sCancer Institute Joins theNCCCPBy Dawn Lagrosa

This past April, Geisinger Medical Center’s (GMC) Cancer In -stitute became one of 14 sites added to the National CancerInstitute Community Cancer Centers Program (NCCCP). Joining

this national network of community cancer centers offers GMC theopportunity to expand its state-of-the-art cancer care and research innortheast Pennsylvania.GMC is a part of Geisinger Health System (Geisinger), which serves

a mostly rural population and has cancer centers in Danville, Wilkes-Barre, State College, and Hazleton. Geisinger takes pride in its innova-tive approach to healthcare delivery to this population, which alsoincludes many elderly patients. In addition, a significant portion isunderserved because of socioeconomic status and transportationproblems. Thanjavur Ravikumar, MD, FACS, director of the Center forSurgical Innovation, and co-chair of the oncology service line at

CANCER CENTER PROFILE


CONFERENCE NEWS

Oncology Nursing Society’s 11th AnnualAdvanced Practice Nursing Conference/Institutes of LearningOrlando, Florida, November 11-14, 2010.See who was there: page 8.

Kimberly Gessner, Holly Gentry, and Marlene Ferguson display copies of The Council ofDads, a book by keynote speaker Bruce Feiler.

Fostering a Dialogue to Improve Patient Care & Outcomes

Submit your cases online today at

www.myelomacases.com

InsideLung CancerStereotactic Radiation for Non–small-cell Lung CancersPage 20

Fast Neutron RadiotherapyPage 25

Continuing Education Maintenance erapy in Patients withAdvanced Non–small-cell Lung CancerPage 30

Breast CancerProlonging Chemotherapy in MetastaticBreast Cancer Improves SurvivalPage 44

TON_December 2010_FINAL_v2_TON 12/8/10 11:47 AM Page Cov1

D

T

f

a

T

v

T

v

H

s

‡

b

So. San Francisco, CA All rights reserved. 10581800 11/10

Announcingthe first and only monoclonal antibody indicated for use inHER2+ metastatic gastric and gastroesophageal junction (GEJ) cancer

to drive outcomes in HER2+ metastatic gastric/GEJ cancer

Boxed WARNINGS Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy

Evaluate cardiac function prior to and during treatment. Discontinue Herceptin for cardiomyopathy

Herceptin can result in serious and fatal infusion reactions and pulmonary toxicity. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

Exposure to Herceptin during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death

Indication Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

S

TON_December 2010_FINAL_v2_TON 12/8/10 11:49 AM Page Cov2

Additional Important Safety Information Exacerbation of chemotherapy-induced neutropenia has also occurred

Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy

The most common adverse reactions associated with Herceptin were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia

Please see brief summary of full Prescribing Information, including Boxed WARNINGS and additional important safety information, on the following pages.

Reference: 1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

Months

Final Median Overall Survival Analysis1

Updated Median Overall Survival Analysis1‡

11.0

13.5

0 3 6 9 12 15

Herceptin plus chemotherapy* (n=298)

Chemotherapy alone* (n=296)

Hazard Ratio = 0.7395% CI: 0.60-0.91

P=0.0038

Hazard Ratio = 0.8095% CI: 0.67-0.97 11.7

13.1

In the ToGA trial†:

• The final overall survival analysis demonstrated a 13.5-month median OS with Herceptin + chemotherapy (cisplatin and either capecitabine or 5-fluorouracil) vs an 11.0-month median OS with chemotherapy alone1

• The updated overall survival analysis demonstrated a 13.1-month median OS with Herceptin + chemotherapy (cisplatin and either capecitabine or 5-fluorouracil) vs an 11.7-month median OS with chemotherapy alone1

• Herceptin should be administered until disease progression or unacceptable toxicity in HER2+ metastatic gastric and GEJ cancer

Herceptin plus chemotherapy* extended median overall survival (OS) in HER2+ metastatic gastric and GEJ cancer1

*Chemotherapy was cisplatin and either capecitabine or 5-FU. ‡ The updated analysis was conducted one year after the final analysis. No P value

was associated with the updated analysis in the Herceptin Prescribing Information because there was no preplanned statistical testing for OS after the final analysis.

†Trastuzumab in gastric cancer.

©2010 Genentech USA, Inc. So. San Francisco, CA All rights reserved. 10581800 11/10

HER2+ metastatic gastric/GEJ cancer

B H

a c

E

H

a

E

t

TON_December 2010_FINAL_v2_TON 12/8/10 11:49 AM Page 1

HERCEPTIN® (trastuzumab)Brief Summary For full Prescribing Information, see package insert.

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY Cardiomyopathy Herceptin administration can result in sub clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline containing chemotherapy regimens. Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function. [see Warnings and Precautions and Dosage and Administration]Infusion Reactions; Pulmonary Toxicity Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of Herceptin administration. Interrupt Herceptin infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions] Embryo-Fetal Toxicity Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. [see Warnings and Precautions, Use in Specific Populations]

INDICATIONS AND USAGE Adjuvant Breast Cancer Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies] breast cancer • as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel • with docetaxel and carboplatin • as a single agent following multi-modality anthracycline based therapy. Metastatic Breast Cancer Herceptin is indicated: • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease. Metastatic Gastric Cancer Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline. Withhold Herceptin for 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and 10% absolute decrease in LVEF from pretreatment values [see Dosage and Administration]. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: • Baseline LVEF measurement immediately prior to initiation of Herceptin • LVEF measurements every 3 months during and upon completion of Herceptin • Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration] • LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy. In Study 1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study 3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity. Among 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the surviving patients had recovery to a normal LVEF (defined as 50%) on continuing medical management at the time of last follow-up. Incidence of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.Table 1 Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies

Incidence of CHF Study Regimen Herceptin Control 1 & 2a ACb Paclitaxel+ Herceptin 2% (32/1677) 0.4% (7/1600) 3 Chemo Herceptin 2% (30/1678) 0.3% (5/1708) 4 ACb Docetaxel+ Herceptin 2% (20/1068) 0.3% (3/1050) 4 Docetaxel+Carbo+ Herceptin 0.4% (4/1056) 0.3% (3/1050)

a Includes 1 patient with fatal cardiomyopathy.b Anthracycline (doxorubicin) and cyclophosphamide

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies

Incidence NYHA I−IV NYHA III−IV Study Event Herceptin Control Herceptin Control 5 Cardiac (AC)b Dysfunction 28% 7% 19% 3% 5 Cardiac (paclitaxel) Dysfunction 11% 1% 4% 1% 6 Cardiac Dysfunctionc 7% N/A 5% N/A

a Congestive heart failure or significant asymptomatic decrease in LVEF.

b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.

c Includes 1 patient with fatal cardiomyopathy.In Study 4, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in the Herceptin containing regimens: (AC-TH: 0.3% (3/1068) and TCH 0.2% (2/1056)) as compared to none in AC-T. Infusion Reactions Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. [see Adverse Reactions] In postmarketing reports, serious and fatal infusion reactions have been reported. Severe reactions which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Herceptin infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered, which may include: epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions. There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications. Embryo-Fetal Toxicity Herceptin can cause fetal harm when administered to a pregnant woman. In post-marketing reports, use of Herceptin during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential. [see Use in Specific Populations, Patient Counseling Information]. Pulmonary Toxicity Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions]. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity. Exacerbation of Chemotherapy-Induced Neutropenia In randomized, controlled clinical trials the per-patient incidences of NCI CTC Grade 3−4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received Herceptin and those who did not. [see Adverse Reactions] HER2 Testing Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Due to differences in tumor histopathology, use FDA-approved tests for the specific tumor type (breast or gastric/gastroesophageal adenocarcinoma) to assess HER2 protein overexpression and HER2 gene amplification. Tests should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. Several FDA-approved commercial assays are available to aid in the selection of breast cancer and metastatic gastric cancer patients for Herceptin therapy. Users should refer to the package inserts of specific assay kits for information on the Intended Use, and the validation and performance of each assay. Limitations in assay precision make it inadvisable to rely on a single method to rule out potential Herceptin benefit. Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) and for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Tables 8 and 10. Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers. Study 7 demonstrated that gene amplification and protein overexpression were not as well correlated as with breast cancer. Treatment outcomes for metastatic gastric cancer (Study 7), based on HER2 gene amplification (FISH) and HER2 protein overexpression (IHC) test results are provided in Table 12. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Cardiomyopathy [see Warnings and Precautions] • Infusion reactions [see Warnings and

Precautions] • Embryo-fetal Toxicity [see Warnings and Precautions] • Pulmonary toxicity [see Warnings and Precautions] • Exacerbation of chemotherapy-induced neutropenia [see Warnings and Precautions] The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration]. In the metastatic gastric cancer setting, the most common adverse reactions ( 10%) that were increased ( 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of treatment on the Herceptin-containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Breast Cancer Studies The data below reflect exposure to Herceptin across three randomized, open-label studies, Studies 1, 2, and 3, with (n= 3355) or without (n= 3308) trastuzumab in the adjuvant treatment of breast cancer. The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in Study 3, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.Table 3 Adverse Reactions for Study 3, All Gradesa:

1 Year Herceptin Observation Adverse Reaction (n= 1678) (n=1708)

CardiacHypertension 64 (4%) 35 (2%)Dizziness 60 (4%) 29 (2%)Ejection Fraction Decreased 58 (3.5%) 11 (0.6%)Palpitations 48 (3%) 12 (0.7%)Cardiac Arrhythmiasb 40 (3%) 17 (1%)Cardiac Failure Congestive 30 (2%) 5 (0.3%)Cardiac Failure 9 (0.5%) 4 (0.2%)Cardiac Disorder 5 (0.3%) 0 (0%)Ventricular Dysfunction 4 (0.2%) 0 (0%)Respiratory Thoracic Mediastinal DisordersCough 81 (5%) 34 (2%)Influenza 70 (4%) 9 (0.5%)Dyspnea 57 (3%) 26 (2%)URI 46 (3%) 20 (1%)Rhinitis 36 (2%) 6 (0.4%)Pharyngolaryngeal Pain 32 (2%) 8 (0.5%)Sinusitis 26 (2%) 5 (0.3%)Epistaxis 25 (2%) 1 (0.06%)Pulmonary Hypertension 4 (0.2%) 0 (0%)Interstitial Pneumonitis 4 (0.2%) 0 (0%)Gastrointestinal DisordersDiarrhea 123 (7%) 16 (1%)Nausea 108 (6%) 19 (1%)Vomiting 58 (3.5%) 10 (0.6%)Constipation 33 (2%) 17 (1%)Dyspepsia 30 (2%) 9 (0.5%)Upper Abdominal Pain 29 (2%) 15 (1%)Musculoskeletal & Connective Tissue DisordersArthralgia 137 (8%) 98 (6%)Back Pain 91 (5%) 58 (3%)Myalgia 63 (4%) 17 (1%)Bone Pain 49 (3%) 26 (2%)Muscle Spasm 46 (3%) 3 (0.2%)Nervous System DisordersHeadache 162 (10%) 49 (3%)Paraesthesia 29 (2%) 11 (0.6%)Skin & Subcutaneous Tissue DisordersRash 70 (4%) 10 (0.6%)Nail Disorders 43 (2%) 0 (0%)Pruritis 40 (2%) 10 (0.6%)General DisordersPyrexia 100 (6%) 6 (0.4%)Edema Peripheral 79 (5%) 37 (2%)Chills 85 (5%) 0 (0%)Aesthenia 75 (4.5%) 30 (2%)Influenza-like Illness 40 (2%) 3 (0.2%)Sudden Death 1 (0.06%) 0 (0%)InfectionsNasopharyngitis 135 (8%) 43 (3%)UTI 39 (3%) 13 (0.8%)Immune System DisordersHypersensitivity 10 (0.6%) 1 (0.06%)Autoimmune Thyroiditis 4 (0.3%) 0 (0%)

a The incidence of Grade 3/4 adverse reactions was <1% in both arms for each listed term.

b Higher level grouping term.The data from Studies 1 and 2 were obtained from 3206 patients, of whom 1635 received Herceptin; the median treatment duration was 50 weeks. The median age was 49 years (range: 24−80); 84% of patients were White, 7% Black, 4% Hispanic, and 4% Asian. In Study 1, only Grade 3−5 adverse events, treatment-related Grade 2 events, and Grade 2−5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following non-cardiac adverse reactions of Grade 2−5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (31% vs. 28%), fatigue (28% vs. 22%), infection (22% vs. 14%), hot flashes (17% vs. 15%), anemia (13% vs. 7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia (3.7% vs. 1.5%). The majority of these events were Grade

2 in severity. In Study 2, data collection was limited to the following investigator-attributed treatment-related adverse reactions: NCI-CTC Grade 4 and 5 hematologic toxicities, Grade 3−5 non-hematologic toxicities, selected Grade 2−5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1−5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment. The following non-cardiac adverse reactions of Grade 2−5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (11% vs. 8.4%), myalgia (10% vs. 8%), nail changes (9% vs. 7%), and dyspnea (2.5% vs. 0.1%). The majority of these events were Grade 2 in severity. Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n = 1056]. The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm. Metastatic Breast Cancer Studies The data below reflect exposure to Herceptin in one randomized, open-label study, Study 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n=222) in patients with metastatic breast cancer. Data in Table 4 are based on Studies 5 and 6. Among the 464 patients treated in Study 5, the median age was 52 years (range: 25−77 years). Eighty-nine percent were White, 5% Black, 1% Asian and 5% other racial/ethnic groups. All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and 12 months were 58% and 9%, respectively. Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28−86 years), 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and

12 months were 31% and 16%, respectively.Table 4 Per-Patient Incidence of Adverse Reactions Occurring in 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Herceptin Arm (Studies 5 and 6)

Herceptin Single + Paclitaxel Herceptin ACb

Agenta Paclitaxel Alone + ACb Alone n = 352 n = 91 n = 95 n = 143 n = 135Body as a Whole Pain 47% 61% 62% 57% 42% Asthenia 42% 62% 57% 54% 55% Fever 36% 49% 23% 56% 34% Chills 32% 41% 4% 35% 11% Headache 26% 36% 28% 44% 31% Abdominal pain 22% 34% 22% 23% 18% Back pain 22% 34% 30% 27% 15% Infection 20% 47% 27% 47% 31% Flu syndrome 10% 12% 5% 12% 6% Accidental injury 6% 13% 3% 9% 4% Allergic reaction 3% 8% 2% 4% 2%Cardiovascular Tachycardia 5% 12% 4% 10% 5% Congestive 7% 11% 1% 28% 7% heart failureDigestive Nausea 33% 51% 9% 76% 77% Diarrhea 25% 45% 29% 45% 26% Vomiting 23% 37% 28% 53% 49% Nausea and vomiting 8% 14% 11% 18% 9% Anorexia 14% 24% 16% 31% 26% Heme & Lymphatic Anemia 4% 14% 9% 36% 26% Leukopenia 3% 24% 17% 52% 34%Metabolic Peripheral edema 10% 22% 20% 20% 17% Edema 8% 10% 8% 11% 5%Musculoskeletal Bone pain 7% 24% 18% 7% 7% Arthralgia 6% 37% 21% 8% 9%Nervous Insomnia 14% 25% 13% 29% 15% Dizziness 13% 22% 24% 24% 18% Paresthesia 9% 48% 39% 17% 11% Depression 6% 12% 13% 20% 12% Peripheral neuritis 2% 23% 16% 2% 2% Neuropathy 1% 13% 5% 4% 4%Respiratory Cough increased 26% 41% 22% 43% 29% Dyspnea 22% 27% 26% 42% 25% Rhinitis 14% 22% 5% 22% 16% Pharyngitis 12% 22% 14% 30% 18% Sinusitis 9% 21% 7% 13% 6%Skin Rash 18% 38% 18% 27% 17% Herpes simplex 2% 12% 3% 7% 9% Acne 2% 11% 3% 3% < 1%Urogenital Urinary tract infection 5% 18% 14% 13% 7%

a Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6.

b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.

M

( In the Herceptin plus chemotherapy arm, the initial d

21 days until d

Herceptin +FC FC N (%)

B

2 (1) 43 (15) 6 (2) 7 (2) 10 ( 3) 1 (

Inflammation 37 (13) 6 (2) 18 (6) 2 (1)

Tract Infections 56 (19) 0 (0) 29 (10) 0 (0) (0) 17 (6) 0 (0)R

Impairment 53 (18) 8 (3) 42 (15) 5 (2)N

P

LVEF Decrease

LVEF <50% decrease decrease

For Studies 1, 2 and 3, events are counted from the beginning o

Studies 1 and 2 regimens: doxorubicin and cyclo-p

Study 4 regimens: doxorubicin and cyclophosphamide

f

S Cumulative Incidence of Time to First LVEF D

i

t

a o

Following the a

In Study 7 (

In a randomized, controlled trial in p N

The most common

p

An increased incidence of d

1

Samples for assessment of

H

t

D I

w

i

Pregnancy: Category D [s

If oligohydramnios occurs,

p a T

phone 1-800-690-6720. [s

Infant monkeys with detectable serum levels of t

Limitations in data collection and d

<

T

• Advise patients to contact a health care professional i

5 pounds in 24 hours, dizziness or loss of consciousness [s Cardiomyopathy]

(


F

Adjuvant Breast Cancer H

(

• as a single agent following multi-modality anthracycline b

N Cardiomyopathy H

o

Herceptin 2% (32/1677) 0.4% (7/1600) ACb

Herceptin 2% (20/1068) 0.3% (3/1050) Docetaxel+Carbo+ Herceptin 0.4% (4/1056) 0.3% (3/1050)

a

I

NYHA III−IV Congestive heart failure or significant asymptomatic

d Anthracycline (doxorubicin or epirubicin) and

c

Severe reactions which

i

Prior to resumption of Herceptin infusion, t

While some patients tolerated Herceptin

i

T

o

The most c

i

(

S

S

1 Year Herceptin Observation

The incidence of Grade 3/4 adverse reactions was <1% in b

received Herceptin; the median t

A

S

The percentages of p

Herceptin Single + Paclitaxel Herceptin ACb

Agenta

n = 352 n = 91 n = 95 n = 143 n = 135B pain 22% 34% 22% 23% 18% injury 6% 13% 3% 9% 4% reaction 3% 8% 2% 4% 2%C

vomiting 8% 14% 11% 18% 9%

edema 10% 22% 20% 20% 17%

neuritis 2% 23% 16% 2% 2%

increased 26% 41% 22% 43% 29%

simplex 2% 12% 3% 7% 9%

infection 5% 18% 14% 13% 7%

a Data for Herceptin single agent were from 4 studies, i

Anthracycline (doxorubicin or epirubicin) and c

Metastatic Gastric Cancer The data below are based on the exposure of 294 patients to Herceptin in combination with a fluoropyrimidine (capecitabine or 5-FU) and cisplatin (Study 7). In the Herceptin plus chemotherapy arm, the initial dose of Herceptin 8 mg/kg was administered on Day 1 (prior to chemotherapy) followed by 6 mg/kg every 21 days until disease progression. Cisplatin was administered at 80 mg/m2 on Day 1 and the fluoropyrimidine was administered as either capecitabine 1000 mg/m2 orally twice a day on Days 1-14 or 5-fluorouracil 800 mg/m2/day as a continuous intravenous infusion Days 1 through 5. Chemotherapy was administered for six 21-day cycles. Median duration of Herceptin treatment was 21 weeks; median number of Herceptin infusions administered was eight.Table 5 Study 7: Per Patient Incidence of Adverse Reactions of All Grades (Incidence 5% between Arms) or Grade 3 /4 (Incidence >1% between Arms) and Higher Incidence in Herceptin Arm

Herceptin +FC FC (N = 294) (N = 290) N (%) N (%)

Body System/ All Grades All GradesAdverse Event Grades 3 / 4 Grades 3/ 4

Investigations Neutropenia 230 (78) 101 (34) 212 (73) 83 (29) Hypokalemia 83 (28) 28 (10) 69 (24) 16 (6) Anemia 81 (28) 36 (12) 61 (21) 30 (10) Thrombocytopenia 47 (16) 14 (5) 33 (11) 8 (3)Blood And Lymphatic System Disorders Febrile Neutropenia _ 15 (5) _ 8 (3)Gastrointestinal Disorders Diarrhea 109 (37) 27 (9) 80 (28) 11 (4) Stomatitis 72 (24) 2 (1) 43 (15) 6 (2) Dysphagia 19 (6) 7 (2) 10 ( 3) 1 ( 1)Body as a Whole Fatigue 102 (35) 12 (4) 82 (28) 7 (2) Fever 54 (18) 3 (1) 36 (12) 0 (0) Mucosal Inflammation 37 (13) 6 (2) 18 (6) 2 (1) Chills 23 (8) 1 ( 1) 0 (0) 0 (0)Metabolism And Nutrition Disorders Weight Decrease 69 (23) 6 (2) 40 (14) 7 (2)Infections And Infestations Upper Respiratory Tract Infections 56 (19) 0 (0) 29 (10) 0 (0) Nasopharyngitis 37 (13) 0 (0) 17 (6) 0 (0)Renal And Urinary Disorders Renal Failure and Impairment 53 (18) 8 (3) 42 (15) 5 (2)Nervous System Disorders Dysgeusia 28 (10) 0 (0) 14 (5) 0 (0)

The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast, metastatic breast cancer, metastatic gastric cancer, or post-marketing experience. Cardiomyopathy Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year Herceptin arm); and in Studies 1 and 2, 23 months in the AC-T arm, 24 months in the AC-TH arm. In Studies 1 and 2, 6% of patients were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF < 50% or

15 point decline in LVEF from baseline to end of AC). Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2).Table 6a Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4

LVEF <50% and Absolute Decrease Absolute from Baseline LVEF Decrease

LVEF 10% 16% <20% and <50% decrease decrease 10% 20%

Studies 1 & 2b AC TH 22.8% 18.3% 11.7% 33.4% 9.2% (n=1606) (366) (294) (188) (536) (148)

AC T 9.1% 5.4% 2.2% 18.3% 2.4% (n=1488) (136) (81) (33) (272) (36)

Study 3 Herceptin 8.6% 7.0% 3.8% 22.4% 3.5% (n=1678) (144) (118) (64) (376) (59)

Observation 2.7% 2.0% 1.2% 11.9% 1.2% (n=1708) (46) (35) (20) (204) (21)

Study 4c TCH 8.5% 5.9% 3.3% 34.5% 6.3% (n=1056) (90) (62) (35) (364) (67)

AC TH 17% 13.3% 9.8% 44.3% 13.2% (n=1068) (182) (142) (105) (473) (141)

AC T 9.5% 6.6% 3.3% 34% 5.5% (n=1050) (100) (69) (35) (357) (58)

a For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization.

b Studies 1 and 2 regimens: doxorubicin and cyclo-phosphamide followed by paclitaxel (AC T) or paclitaxel plus Herceptin (AC TH).

c Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC T) or docetaxel plus Herceptin (AC TH); docetaxel and carboplatin plus Herceptin (TCH).

Figure 1 Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is initiation of paclitaxel or Herceptin + paclitaxel therapy.

Figure 2 Study 3: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is the date of randomization.

Figure 3 Study 4: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is the date of randomization.

The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I−IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines. In Study 7, 5.0% of patients in the Herceptin plus chemotherapy arm compared to 1.1% of patients in the chemotherapy alone arm had LVEF value below 50% with a

10% absolute decrease in LVEF from pretreatment values. Infusion Reactions During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusional toxicity was required in <1% of patients. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and asthenia. Infusional toxicity occurred in 21% and 35% of patients, and was severe in 1.4% and 9% of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported. Anemia In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2-5 anemia (12.5% vs. 6.6% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm the overall incidence of anemia was 28% compared 21% and of NCI CTC Grade 3/4 anemia was 12.2% compared to 10.3%. Neutropenia In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4−5 neutropenia (2% vs. 0.7% [Study 2]) and of selected Grade 2−5 neutropenia (7.1% vs. 4.5% [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm, the incidence of NCI CTC Grade 3/4 neutropenia was 36.8% compared to 28.9%; febrile neutropenia 5.1% compared to 2.8%. Infection The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2−5 infection/febrile neutropenia

(22% vs. 14% [Study 1]) and of selected Grade 3−5 infection/febrile neutropenia (3.3% vs. 1.4%) [Study 2]), were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract. In Study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3−4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms. In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelo suppressive chemo-therapy as compared to chemo therapy alone. Pulmonary Toxicity Adjuvant Breast Cancer Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2−5 pulmonary toxicity (14% vs. 5% [Study 1]) and of selected NCI-CTC Grade 3−5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4% vs. 1% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI-CTC Grade 2−5: 12% vs. 4% [Study 1]; NCI-CTC Grade 2−5: 2.5% vs. 0.1% [Study 2]). Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone. In Study 3, there were 4 cases of interstitial pneumonitis in Herceptin-treated patients compared to none in the control arm. Metastatic Breast Cancer Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distress syndrome. For a detailed description, see Warnings and Precautions. Thrombosis/Embolism In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (3.0% vs. 1.3% [Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]). Diarrhea Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2−5 diarrhea (6.2% vs. 4.8% [Study 1]) and of NCI-CTC Grade 3−5 diarrhea (1.6% vs. 0% [Study 2]), and of Grade 1−4 diarrhea (7% vs. 1% [Study 3]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3−4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1−4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea. An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer. Renal Toxicity In Study 7 (metastatic gastric cancer) on the Herceptin-containing arm as compared to the chemotherapy alone arm the incidence of renal impairment was 18% compared to 14.5%. Severe (Grade 3/4) renal failure was 2.7% on the Herceptin-containing arm compared to 1.7% on the chemotherapy only arm. Treatment discontinuation for renal insufficiency/failure was 2% on the Herceptin-containing arm and 0.3% on the chemotherapy only arm. In the postmarketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported. The time to onset ranged from 4 months to approximately 18 months from initiation of Herceptin therapy. Pathologic findings included membranous glomerulonephritis, focal glomerulosclerosis, and fibrillary glomerulonephritis. Complications included volume overload and congestive heart failure. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to Herceptin was detected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experience an allergic reaction. Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer. The incidence of antibody formation is highly dependent on the sensitivity and the specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Herceptin with the incidence of antibodies to other products may be misleading. Post-Marketing Experience The following adverse reactions have been identified during post approval use of Herceptin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Infusion reaction [see Warnings and Precautions] • Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see Warnings and Precautions] • Glomerulopathy [see Adverse Reactions] DRUG INTERACTIONS In Study 5, the mean serum trough concentration of trastuzumab was consistently elevated approximately 1.5-fold, when administered in combination with paclitaxel as compared to trough concentrations of trastuzumab when administered in combination with an anthracycline and cyclophosphamide. In other pharmacokinetic studies, where Herceptin was administered in combination with paclitaxel, docetaxel or doxorubicin, Herceptin did not alter the plasma concentrations of these chemotherapeutic agents, or the metabolites that were analyzed. In a drug interaction substudy conducted in patients in Study 7, the pharmacokinetics of cisplatin,

capecitabine and their metabolites were not altered when administered in combination with Herceptin. USE IN SPECIFIC POPULATIONS Pregnancy: Category D [see Warnings and Precautions, Nonclinical Toxicology] Herceptin can cause fetal harm when administered to a pregnant woman. In post-marketing reports use of Herceptin during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. These case reports described oligohydramnios in pregnant women who received Herceptin either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after Herceptin was stopped. In one case, Herceptin therapy resumed after the amniotic fluid index improved, and oligohydramnios recurred. Monitor women exposed to Herceptin during pregnancy for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. The efficacy of IV hydration in management of oligohydramnios due to Herceptin exposure is not known. Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy. Encourage pregnant women with breast cancer who are using Herceptin to enroll in MotHER-the Herceptin Pregnancy Registry: phone 1-800-690-6720. [see Patient Counseling Information]. No teratogenic effects were observed in offspring from reproduction studies in cynomolgus monkeys at doses up to 25 times the recommended weekly human dose of 2 mg/kg trastuzumab. In mutant mice lacking HER2, embryos died in early gestation. Trastuzumab exposure was reported at delivery in offspring of cynomolgus monkeys treated during the early (Days 20-50 of gestation) or late (Days 120-150 of gestation) fetal development periods, at levels of 15 to 28% of the maternal blood levels. Nursing Mothers It is not known whether Herceptin is excreted in human milk, but human IgG is excreted in human milk. Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the breast milk of lactating cynomolgus monkeys given 12.5 times the recommended weekly human dose of 2 mg/kg of Herceptin. Infant monkeys with detectable serum levels of trastuzumab did not have any adverse effects on growth or development from birth to 3 months of age; however, trastuzumab levels in animal breast milk may not accurately reflect human breast milk levels. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from Herceptin, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of trastuzumab and the importance of the drug to the mother. Pediatric Use The safety and effectiveness of Herceptin in pediatric patients has not been established. Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in Studies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients <65 years of age for metastatic disease and adjuvant treatment. In Study 7 (metastatic gastric cancer), of the 294 patients treated with Herceptin 108 (37%) were 65 years of age or older, while 13 (4.4%) were 75 and over. No overall differences in safety or effectiveness were observed. OVERDOSAGE There is no experience with overdosage in human clinical trials. Single doses higher than 8 mg/kg have not been tested. PATIENT COUNSELING INFORMATION • Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Boxed Warning Cardiomyopathy]. • Advise pregnant women and women of childbearing potential that Herceptin exposure can result in fetal harm [see Warnings and Precautions and Use in Specific Populations]. • Advise women of childbearing potential to use effective contraceptive methods during treatment and for a minimum of six months following Herceptin [see Warnings and Precautions]. • Advise nursing mothers treated with Herceptin to discontinue nursing or discontinue Herceptin, taking into account the importance of the drug to the mother [see Use in Specific Populations]. • Encourage women who are exposed to Herceptin during pregnancy to enroll in MotHER- the Herceptin Pregnancy Registry (1-800-690-6720) [see Warnings and Precautions and Use in Specific Populations].

HERCEPTIN® [trastuzumab]Manufactured by:Genentech, Inc.A Member of the Roche Group1 DNA WaySouth San Francisco, CA 94080-4990

Initial US Approval: September 1998Revision Date: October 29, 2010Herceptin® is a registered trademark of Genentech, Inc.HER0000111000©2010 Genentech, Inc.


www.TheOncologyNurse.com4 December 2010 I VOL 3, NO 8

Editorial Board

EDITOR-IN-CHIEFBeth Faiman,RN, MSN, APRN,BC, AOCNCleveland Clinic TaussigCancer InstituteCleveland, OH

Elizabeth Bilotti,RN, MSN, APRN,BC, OCNJohn Theurer Cancer CenterHackensack UniversityMedical CenterHackensack, NJ

Catherine S.Bishop, DNP, NP,AOCNPVienna, VA

Deena DamskyDell, RN, MSN,AOCN, BCFox Chase Cancer CenterPhiladelphia, PA

Wendy DiSalvo,DNP, APRN, AOCNGenentechNew London, NH

DeniceEconomou, RN,MN, CNS, AOCNCity of Hope NationalMedical CenterDuarte, CA

ConstanceEngelking, RN,MS, CNS, OCNThe CHE ConsultingGroup, Inc.Mt. Kisco, NY

Amy Ford, RN,BSN, OCNInnovexDallas, TX

Sharon S. Gentry,RN, MSN, AOCNDerrick L. Davis ForsythRegional Cancer CenterWinston-Salem, NC

Cassandra J.Hammond, RN,MSN, CRNPAvid Education Partners,LLCSharpsburg, MD

Shannon Hazen,RN, BSN, OCNNovant HealthPresbyterian CancerCenterCharlotte, NC

Patricia IrouerHughes, RN, MSN,BSN, OCNPiedmount HealthcareRex, GA

Taline Khoukaz,NP, MSN, ACNP-CUniversity of SouthernCaliforniaNorris Cancer Center &HospitalLos Angeles, CA

Sandra E. Kurtin,RN, MS, AOCN,ANP-CArizona Cancer CenterTucson, AZ

Elizabeth Lima,PA-CCleveland Clinic TaussigCancer InstituteCleveland, OH

Ann McNeill,MSN, RN, NP-C,OCNThe Cancer Center atHackensack University Medical CenterHackensack, NJ

Kena C. Miller,RN, MSN, FNPRoswell Park CancerInstituteBuffalo, NY

Patricia Molinelli,MS, RN, APN-C,AOCNSSomerset Medical CenterSomerville, NJ

Dolores “Jeff”Nordquist, RN, MS,CS, FNPMayo ClinicRochester, MN

MelindaOberleitner, RN,DNS, APRN, CNSCollege of Nursing andAllied Health ProfessionsUniversity of LouisianaLafayette, LA

Gary Shelton,MSN, ARNP,AOCNNYU Cancer InstituteNew York, NY

Lori Stover, RN,BSNWestern PennsylvaniaCancer Institute Pittsburgh, PA

Pamela HallquistViale, RN, MS,CS, ANP, AOCNSaratoga, CA

Connie Visovsky,RN, PhD, APRNUniversity of NebraskaCollege of NursingOmaha, NE

Rita Wickham,OCN, PhD, RNRush University College ofNursingRush-Presbyterian-St. Luke’s Medical CenterChicago, IL

Karla Wilson, RN,MSN, FNP-C, CPONCity of Hope NationalMedical CenterDuarte, CA

PharmacyJohn F. Aforismo,BSc Pharm, RPh,FASCPR. J. Health SystemsInternational, LLCWethersfield, CT

NutritionKaren Connelly,RD, CSOSomerset Medical CenterSomerville, NJ

Patient AdvocatePeg FordCoronado, CA

Social WorkCarolyn Messner,DSW, MSW, LCSW-R, BCDCancerCareNew York, NY

Managed Care andPharmaceuticalManagementBurt Zweigenhaft,BSBioPharma Partners LLCNew York, NY

Isabell Castellano, RNBristol-Myers Squibb Children’s HospitalRobert Wood Johnson University HospitalNew Brunswick, NJ

Jeanne Westphal, RNMeeker County Memorial HospitalLitchfield, MN


TON_December 2010_FINAL_TON 12/6/10 11:19 AM Page 5

CONFERENCE NEWS: ONS APN/IOL8 Faces at the conference9 Prophylactic minocycline keeps

cetuximab-induced rash at bay10 Collaborative program trains oncology

specialist nurses26 Telephone support increases adherence

to IV chemotherapy for recurrent ovariancancer

28 Survey shows gaps in oncology nurses’knowledge about cardiotoxicity of cancerdrugs

CANCER COMPLICATIONS16 Prompt pain relief for vertebral

compression fractures with balloonkyphoplasty

LUNG CANCER20 Stereotactic radiation may be as effective

as surgery for some non–small-cell lungcancers

25 Fast neutron radiotherapy may be safeand effective for lung cancer patients

32 Low-dose CT screening found to reducelung cancer deaths in large study

CONTINUING EDUCATION30 Maintenance therapy in patients with

advanced non–small-cell lung cancer

BREAST CANCER44 Prolonging chemotherapy in metastatic

breast cancer improves survival

44 Tamoxifen may confer a limited benefit in older women with early-stage breast cancer

45 PARP inhibitor improves survival in triple-negative breast cancer

DEPARTMENTS24 International News

36 Oncology Drug Codes

46 Nursing Life

49 Meetings

CARE COORDINATION1 City-wide patient navigation network

coordinates Washington, DC, cancer care

NAVIGATION TRAINING1 Center provides platform for discussion of

cancer survivorship, navigation, and policy

PSYCHOSOCIAL ISSUES3 Most oncology nurses unfamiliar

with IOM report on caring for the whole patient

4 Integrative psychooncology services: how the Cleveland Clinic did it

BREAST CANCER2 Patient navigation improves

mammography rates in the inner city

SURVIVORSHIP4 Survivors often dissatisfied with

breast-conserving treatment results

December 2010 • VOL 3, NO 8

PUBLISHING STAFFPublisherPhilip [email protected]

Editorial DirectorKaren [email protected]

Associate EditorDawn [email protected]

Director, Client ServicesJohn W. [email protected]

Production ManagerStephanie Laudien

Business ManagerBlanche [email protected]

Executive AdministratorAndrea Boylston

Circulation [email protected]

Editorial Contact:Telephone: 732-992-1891 Fax: 732-656-7938

The Oncology Nurse®-APN/PA, ISSN 1944-9798 (print);ISSN 1944-9801 (online) is published 8 times a year byGreen Hill Healthcare Communications, LLC, 241Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831.Telephone: 732.656.7935. Fax: 732. 656.7938. Copyright©2010 by Green Hill Health care Com munications,LLC. All rights reserved. The Oncology Nurse®-APN/PAlogo is a registered trademark of Green Hill HealthcareCommunications, LLC. No part of this publication maybe reproduced or transmitted in any form or by anymeans now or hereafter known, electronic or mechan-ical, including photocopy, recording, or any informa-tional storage and retrieval system, without writtenpermission from the Publisher. Printed in the UnitedStates of America.

EDITORIAL CORRESPONDENCE should beaddressed to EDITORIAL DIRECTOR, The OncologyNurse®-APN/PA, 241 Forsgate Drive, Suite 205C,Monroe Twp, NJ 08831. E-mail: [email protected] SUBSCRIPTION RATES: United Statesand possessions: individuals, $105.00; institutions,$135.00; single issues, $17.00. Orders will be billed atindividual rate until proof of status is confirmed. Pricesare subject to change without notice. Correspondenceregarding permission to reprint all or part of any articlepublished in this journal should be addressed toREPRINT PERMISSIONS DEPARTMENT, GreenHill Healthcare Communications, LLC, 241 ForsgateDrive, Suite 205C, Monroe Twp, NJ 08831. The ideasand opinions expressed in The Oncology Nurse®-APN/PAdo not necessarily reflect those of the Editorial Board, theEditorial Director, or the Publisher. Publication of anadvertisement or other product mention in The OncologyNurse®-APN/PA should not be construed as an endorse-ment of the product or the manufacturer’s claims.Readers are encouraged to contact the manufacturer withquestions about the features or limitations of the productsmentioned. Neither the Editorial Board nor the Publisherassumes any responsibility for any injury and/or damageto persons or property arising out of or related to any useof the material contained in this periodical. The reader isadvised to check the appropriate medical literature andthe product information currently provided by the manu-facturer of each drug to be administered to verify thedosage, the method and duration of administration, orcontraindications. It is the responsibility of the treatingphysician or other healthcare professional, relying onindependent experience and knowledge of the patient, todetermine drug dosages and the best treatment for thepatient. Every effort has been made to check generic andtrade names, and to verify dosages. The ultimate respon-sibility, however, lies with the prescribing physician.Please convey any errors to the Editorial Director.

CONTENTS

Two new reports call forchanges in education toensure that healthcare pro-

fessionals have the competenciesnecessary to work in an increasinglycomplex healthcare system. Sinceoncology is one of the most complexand rapidly advancing areas of med-icine, their recommendations haveimplications for oncology nursesand our colleagues.In a report by the Lancet Com -

mission (Frenk J, et al. Lancet. Nov26, 2010. Epub ahead of print), theauthors propose a number of in -structional and institutional re -

forms, including “team-based education to break downprofessional silos.” A report by the Institute of Medicine specifically address-

es nursing education and practice (The Future of Nursing:Leading Change, Advancing Health; 2010). “Nurses’ roles,responsibilities, and education should change significantly

to meet the increased demand for care that will be createdby health care reform and to advance improvements inAmerica’s increasingly complex health system,” the reportstates. Among the changes they recommend are removingscope of practice barriers and improving the education sys-tem to include the creation of a residency program. Thereport also calls for nursing associations, schools, and otherorganizations to “provide nurses greater opportunities togain leadership skills and put them into practice.”In many ways, oncology nurses are ahead of the curve

on these issues and are already putting some of theseideas into practice. Many of us have advanced educationand credentials; we work closely with our colleagues inmultidisciplinary teams; and we play an active role inpatient and nursing education throughout the continu-um of cancer care. Oncology nurses are well positionedto take a leadership role in advancing the profession andensuring that patients receive the highest-quality care.The Oncology Nurse will continue to provide reports onthe latest advances in nursing practice and cancer care tohelp our readers meet the challenges of practice in achanging healthcare environment. �

Beth Faiman, RN,MSN, APRN,BC, AOCNEditor-in-Chief

Green Hill Healthcare Communications LLCGreen Hill Healthcare Communications, LLCHGYour Innovative Partners in Medical Media™

™

241 Forsgate Drive, Suite 205CMonroe Twp, NJ 08831

FROM THE EDITOR

6 December 2010 I VOL 3, NO 8 www.TheOncologyNurse.com




Between pages 34 and 35


WillWeexhaust all possibilities.

Celgene Patient Support® provides free and personalized assistance with patients’ access andreimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support®

Specialist will streamline access to our products by helping you and your patients with:

• Benefits investigation

• Prior authorization

• Appeal support

• Medicare

• Co-pay assistance

• Prescription status

• Free medication program

• Celgene products and restricted distribution programs (RevAssist® or S.T.E.P.S.®)

To Contact Celgene Patient Support®:

Call: 1-800-931-8691

E-mail: [email protected]

Fax: 1-800-822-2496

Visit: www.CelgenePSC.com

Monday−Friday, 8:00 AM to 7:00 PM ET

We will…because patients are our priority.

©2010 Celgene Corporation 05/10 CELG10100T

Celgene Patient Support®, RevAssist®, and S.T.E.P.S.® are registered trademarks of Celgene Corporation.

4 out of 5 patients who requested assistance fromCelgene Patient Support ® received their medication.

718.482.1800 1



Conference News

Faces at the Conference

Photos by Mark Losh • For more photos go to www.TheOncologyNurse.com

ONCOLOGY NURSING SOCIETY’S 11TH ANNUAL ADVANCED PRACTICE NURSING CONFERENCE/INSTITUTES OF LEARNING

Orlando, Florida, November 11-14, 2010.

Judy Sigmon catches up on the latest in mastectomy bras and prostheses.

Millie Toth celebrates breast cancer awareness with pink gloves.

Congratulations to Tanya Laudick of Greeley, Colorado, winner of our iPad giveaway.

Michelle Blanca and Sylvia Robertson point out what they are learning.

Karen Stephenson stops by to chat with The OncologyNurse-APN/PA Editor-in-Chief Beth Faiman.

Bobbie Piccolo checks out a contemporary infusion chair. Maureen Berry, Michael Rehbein, and Pamela Grant-Navarro take time out for coffee.

Magda Ostos-Germain and Ali Khan pose for our camera.

Ami Rowe tests state-of-the-art technology.


ORLANDO—Breakthrough pain incancer patients can be managed easilyand effectively with fentanyl pectin nasalspray, according to new data.

Minocycline, given before the start oftreatment with cetuximab and chemo -radiotherapy, plus topical pimecrolimusas needed, can reduce the severity ofcetuximab-induced skin toxicity inpatients with non–small-cell lung can-cer (NSCLC), according to researchersfrom The Netherlands.

Cetuximab, a chimeric monoclonalantibody that binds to the extracellu-lar domain of the epidermal growth

factor receptor, has shown activity inpatients with metastatic colorectalcancer, in addition to patients withNSCLC, but its potential for severeskin toxicity may cause some patientsto abandon their treatment, saidWilma Uyterlinde, MANP, a nursepractitioner at the Netherlands Can -cer Institute in Amsterdam.

In 2008, oncologists at the institutebegan to test the feasibility of combin-ing cetuximab with concurrent chemo -radiation in their patients with locallyadvanced NSCLC.

“We added cetuximab to our treat-ment because of the promising effects itwas shown to have in colorectal cancerpatients, and when we did so, we saw alot of grade 3 skin toxicity, so we con-ferred with a dermatologist and anoncologist and we came up with a newprotocol to see if we could reduce it,”said Uyterlinde, who specializes in tho-racic oncology.

To test their protocol, the re searchersdivided patients into two groups. All

patients received cetuximab onceweekly for 6 weeks along with daily cis-platin and radiotherapy. The 12patients in group 1 were treated ondemand after the appearance of an

acneiform rash. The 14 patients ingroup 2 received prophylactic oralminocycline, 100 mg/day for 45 days,and, if necessary, topical pimecrolimus,1%, twice daily.

Toxicity was scored according to theCommon Toxicity Criteria for AdverseEvents, version 3.0.

In the first group, 11 of 12 patients

ONS APN/IOL

Prophylactic Minocycline Keeps Cetuximab-induced Rash at BayBy Fran Lowry

December 2010 I VOL 3, NO 8 9www.TheOncologyNurse.com

Conference News

Help reduce the risk of infection in patients receiving moderate-risk* chemotherapy regimens

Act before febrile neutropenia strikes

Potential consequences of febrile neutropenia may be serious and can impact patient care

First- and every-cycle Neulasta® achieved:

� 94% reduction in febrile neutropenia

(17% placebo vs 1% Neulasta®; P < 0.001).1,2

� 93% reduction in febrile neutropenia–

related hospitalization (14% placebo

vs 1% Neulasta®; P < 0.001).1,2

� 80% reduction in febrile neutropenia–

related IV anti-infective use (10% placebo

vs 2% Neulasta®; P < 0.001).1,2

Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Neulasta® is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Important Safety InformationDo not administer Neulasta® to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Splenic rupture, including fatal cases, can occur following the administration of Neulasta®. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta®.

Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta®. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta® for ARDS. Discontinue Neulasta® in patients with ARDS.

Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta®. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta® in patients with serious allergic reactions.

Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta®. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

The granulocyte colony-stimulating factor (G-CSF) receptor, through which pegfilgrastim and filgrastim act, has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

Bone pain and pain in extremity occurred at a higher incidence in Neulasta®-treated patients as compared with placebo-treated patients.

Please see brief summary of Neulasta® Prescribing Information on the adjacent page.

* Regimens associated with 17% risk of febrile neutropenia.

References: 1. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 2. Neulasta® (pegfilgrastim) Prescribing Information. Thousand Oaks, Calif: Amgen.

© 2010 Amgen. All rights reserved. MC49047-A-1 04-10 www.neulasta.com


“If we give minocyclineprophylactically and donot wait for the rash toappear, we manage toreduce the skin toxicity toa maximum of grade 2.”

—Wilma Uyterlinde, MANP


developed grade 2 or 3 acneiform rash,and one patient discontinued treatmentbecause of the rash. In the second group,three of 14 patients developed grade 2rash, and none of the patients developedgrade 3 rash. This represents a significantdifference be tween the groups (P =.001), Uyter linde said.

“In the cohort that did not get prophy-lactic treatment, we sometimes had tosend patients to a specialized hospital fortheir skin toxicity because it was so bad,and we had to stop treatment with cetux-imab because of the rash,” Uyterlindenoted. “If we give minocycline prophy-lactically and do not wait for the rash to

appear, we manage to reduce the skintoxicity to a maximum of grade 2.”

She noted that controlling theacneiform rash did not compromise theeffectiveness of cetuximab.

“It has not been proven that devel-oping a rash means that cetuximab isworking,” she said. “This is what they

say, but it has never really been proven.That is a hypothesis. Controlling therash works by a different mechanismand does not prevent the cetuximabfrom working on the tumor.”

The protocol has now become theinstitute’s standard for use in patientswith other types of cancer undergoingtreatment with cetuximab, she said. �

ORLANDO—Despite the need fornurses with specialized oncology knowl-edge to care for the growing populationof cancer patients and survivors, fewgraduate oncology nursing programs cur-rently exist. A collaboration betweenThe Ohio State University Comp re -hensive Cancer Center –The JamesCancer Hospital (OSUCCC-James) andthe university’s College of Nursing(CON) has been established to help ful-fill the need for nurses with specializedoncology education.

The collaboration between the can-cer center and the college, described in aposter presented by Deborah Hanes,RN, CNS, and her colleagues, has re -sulted in a graduate oncology nursingprogram and an oncology clinical nursespecialist internship. The graduate nurs-ing program will provide curriculum andclinical practicum sites by the CON andOSUCCC-James. The internship willtrain registered nurses with at least 3years of experience as a registered nurseto become oncology clinical nurse spe-cialists. Interns will be full-time employ-ees of OSUCCC-James and will pursuepart-time study following the CON cur-riculum; program participants will re -ceive tuition reimbursement.

The framework for all educationalexperiences will be the cancer continu-um, with emphasis on survivorship.Both the graduate program and theinternship are based on adult learningtheory. Students’ success rates on theAdvanced Oncology Clinical NurseSpecialist examination will be onemeasure of the program’s success.

The developers of the program antic-ipate that it will boost oncology recruit-ment and retention, and that patientswill benefit from care based on gradu-ate-level oncology nursing education. �


Conference News

BRIEF SUMMARY OF PRESCRIBING INFORMATIONNeulasta® (pegfilgrastim) injection, for subcutaneous use

INDICATIONS AND USAGENeulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

CONTRAINDICATIONSDo not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

WARNINGS AND PRECAUTIONSSplenic RuptureSplenic rupture, including fatal cases, can occur following the administration of Neulasta. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta.

Acute Respiratory Distress SyndromeAcute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta, for ARDS. Discontinue Neulasta in patients with ARDS.

Serious Allergic ReactionsSerious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta in patients with serious allergic reactions. Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Use in Patients With Sickle Cell DisordersSevere sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

Potential for Tumor Growth Stimulatory Effects on Malignant CellsThe granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim and filgrastim act has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

ADVERSE REACTIONSThe following serious adverse reactions are discussed in greater detail in other sections of the Brief Summary:

Warnings and Precautions] Warnings

and Precautions] Warnings and Precautions]

Warnings and Precautions]

Warnings and Precautions]The most common adverse reactions occurring in 5% of patients and with a between-group difference of 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity.

Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Neulasta clinical trials safety data are based upon 932 patients receiving Neulasta in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received Neulasta after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.The following adverse reaction data in Table 1 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer

pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. In animal reproduction studies, when pregnant rabbits received pegfilgrastim at cumulative doses approximately 4 times the recommended human dose (based on body surface area), increased embryolethality and spontaneous abortions occurred. Signs of maternal toxicity (reductions in body weight gain/food consumption) and decreased fetal weights occurred at maternal doses approximately equivalent to the recommended human dose (based on body surface area). There were no structural anomalies observed in rabbit offspring at any dose tested. No evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area).Women who become pregnant during Neulasta treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Nursing MothersIt is not known whether pegfilgrastim is secreted in human milk. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. Caution should be exercised when administered to a nursing woman.

Pediatric UseSafety and effectiveness of Neulasta in pediatric patients have not been established. The adverse reaction profile and pharmacokinetics of pegfilgrastim were studied in 37 pediatric patients with sarcoma. The mean (± standard

0-inf) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13), and 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11). The terminal elimination half-lives of the corresponding age groups were 20.2 (± 11.3) hours, 21.2 (± 16.0) hours, and 30.1 (± 38.2) hours, respectively. The most common adverse reaction was bone pain.

Geriatric UseOf the 932 patients with cancer who received Neulasta in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

Renal ImpairmentIn a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose adjustment in patients with renal dysfunction is not necessary.

DOSAGE AND ADMINISTRATIONThe recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle in adults. Do not administer Neulasta between 14 days before and 24 hours after administration of cytotoxic chemotherapy.Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Neulasta if discoloration or particulates are observed.NOTE: The needle cover on the single-use prefilled syringe contains dry natural rubber (latex); persons with latex allergies should not administer this product.

This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 5,582,823; 5,580,755, as well as other patents or patents pending.

receiving docetaxel 100 mg/m2 every 21 days. (Study 3). A total of 928 patients were randomized to receive either 6 mg Neulasta (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and <1% Asian, Native American or other.Bone pain and pain in extremity occurred at a higher incidence in Neulasta-treated patients as compared with placebo-treated patients.

Table 1. Adverse Reactions With ≥ 5% Higher Incidence in Neulasta Patients Compared to Placebo in Study 3

System Organ Class Preferred Term

Placebo (N = 461)

Neulasta 6 mg SC on Day 2

(N = 467)

Musculoskeletal and connective tissue disorders

Bone pain 26% 31%

Pain in extremity 4% 9%

LeukocytosisIn clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving Neulasta. No complications attributable to leukocytosis were reported in clinical studies.

ImmunogenicityAs with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

Postmarketing ExperienceThe following adverse reactions have been identified during post approval use of Neulasta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal relationship to Neulasta.Gastro-intestinal disorders: Warnings and Precautions]Blood and lymphatic system disorder: Sickle cell crisis

Warnings and Precautions]Respiratory, thoracic, and mediastinal disorder: ARDS

Warnings and Precautions]General disorders and administration site conditions: Injection site reactionsSkin and subcutaneous tissue disorders: Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, and urticaria, Sweet’s syndrome, generalized erythema and

Warnings and Precautions]

DRUG INTERACTIONSNo formal drug interaction studies between Neulasta and other drugs have been performed. Increased hematopoietic activity of the bone marrow in response to growth factor therapy may result in transiently positive bone-imaging changes. Consider these findings when interpreting bone-imaging results.

USE IN SPECIFIC POPULATIONSPregnancyPregnancy Category CThere are no adequate and well-controlled studies in pregnant women. Pegfilgrastim was embryotoxic and increased pregnancy loss in pregnant rabbits that received cumulative doses approximately 4 times the recommended human dose (based on body surface area). Signs of maternal toxicity occurred at these doses. Neulasta should be used during

Neulasta® (pegfilgrastim)

Manufactured by:Amgen Inc.One Amgen Center DriveThousand Oaks, California 91320-1799

© 2010 Amgen Inc. All rights reserved.www.neulasta.com1-800-77-AMGEN (1-800-772-6436)

v 11.0

Prophylactic Minocycline Keeps Cetuximab-induced... Continued from page 9

Conference News continued on page 26

CollaborativeProgram TrainsOncologySpecialistNursesBy Karen Rosenberg


To learn more about Balloon Kyphoplasty, visit our website

at www.kyphon.com.

KYPHON® Balloon Kyphoplasty

The complication rate with KYPHON® Balloon Kyphoplasty has been demonstrated to be low. As with all surgical procedures, there are risks associated with the procedure, including serious complications, and though rare, some of which can be fatal. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices’ Instructions for Use included with the product.© 2009 Medtronic Spine LLC. All Rights Reserved. 16003611_001 rev 1

Tom Callaghan experienced debilitating pain due to spinal fractures caused by multiple myeloma. He underwent a minimally invasive procedure, Balloon Kyphoplasty, to treat the spinal fractures.

“After my balloon kyphoplasty, I’m walking pain-free again.”



Genetic Testing

demonstrated a consistent statisticallink to distant breast cancer recurrence(Figure 1)2 as well as to the degree ofresponse to chemotherapy (Figure 2).3An algorithm is used to calculate a“recurrence score” (RS) from theexpression results for each of 16 cancer-related genes. The RS ranges from zeroto 100. Cutoff points for RS risk groupsare defined: low risk, <18; intermediaterisk, 18 to 30; and high risk, ≥31. TheRS provides information that is inde-pendent from age, size, and grade of thetumor.2 This information helps tailortreatment for the individual patient. Inaddition, the RS is a more significantpredictor of distant recurrence-free sur-vival independent of age and tumorsize.2 Assigning Individualized Optionsfor Treatment (Rx), a multi-institu-tional trial known as TAILORx, aimsto determine, more specifically, howpredictive the assay is for the interme-diate-risk RS group.4 The manufacturerhas Clinical Laboratory ImprovementAmendments certification, and strictly

adheres to College of American Path -ology standards.The 21-gene assay is for use in

patients with stage I or II, node-nega-tive, ER-positive breast cancer who willbe treated with hormone therapy. In2007, the assay was included in the2007 American Society of ClinicalOncology clinical guidelines on the useof tumor markers in breast cancer.5 In2008, the National ComprehensiveCancer Network incorporated the assayinto its breast cancer clinical practiceguidelines.6 These inclusions reinforcethe significance of molecular diagnosticsin breast cancer treatment planning and,in particular, the potential value of theindividualized information provided.After the assay became available to

clinicians, the manufacturer discov-ered that 4% to 6% of specimens sentfor testing that were ER-positive onimmunohistochemistry (IHC) stainingwere not ER-positive by RT-PCR. Inaddition, 9% to 20% of specimens thatwere ER-negative by IHC were ER-pos-

itive by RT-PCR. This raised concern:Are there women who could benefitfrom hormone therapy who are notbeing identified? To answer this ques-tion, the company started includingindividual quantitative ER, PR, andHER2 scores as part of its reports in2008. It now offers an ER qualifier pro-gram to guide decisions on testing spec-imens, based on medical necessity asdetermined by the referring physician, ifthe ER status by IHC is in question.Recently presented information sug-

gests increased applications for the 21-gene assay. Three studies have shownthat it is also informative for womenwith node-positive, hormone receptor(HR)-positive, invasive breast cancer.Goldstein and colleagues looked at theprognostic ability of the assay in HR-positive operable breast cancer with oneto three positive nodes. They found thata low RS is predictive of an excellentoutcome at 5 years, and that a low RS isa common finding in these patients(49%).7 The researchers suggested thatpatients with a low RS might be candi-dates for a shorter course of chemother-apy, plus hormonal therapy; and that ahigh score may be used to select patientswho need more aggressive chemothera-py or who would be candidates for clin-ical trials evaluating novel agents.7Dowsett and colleagues, on behalf of

the Arimidex, Tamoxifen, Alone or inCombination (ATAC) Trialists’ Group,presented a follow-up study referred toas transATAC at the San AntonioBreast Cancer Symposium in 2008.8They looked at the risk of distant recur-rence using the 21-gene assay in post-menopausal breast cancer patients withand without positive nodes who weretreated with either tamoxifen or anas-trozole, an aromatase inhibitor. Pre -viously, the RS score had only beenvalidated in patients treated withtamoxifen; in the present day, an aro-matase inhibitor is usually the en -docrine treatment of choice in post-menopausal women. The researchersevaluated 302 node-positive womenand 872 node-negative women. Theyconcluded that the RS for women treat-ed with tamoxifen may be applied forthose treated with anastrozole withadjustment for the lower risk of recur-rence seen with aromatase inhibitors.They further concluded that the RS isan independent predictor of diseaserecurrence in node-positive as well as

node-negative HR-positive patients(Figure 3, page 14).8Albain and colleagues, on behalf of the

Breast Cancer Intergroup of NorthAmerica, presented results of a retrospec-tive analysis of a randomized study(SWOG 8814) of the prognostic and pre-dictive value of the RS in postmeno -pausal women with node-positive, ER-positive breast cancer.9 They investigatedspecifically whether the RS was prognos-tic in women treated with tamoxifenalone and whether it identified womenwho could possibly avoid anthracycline-based chemotherapy (cyclo phospha -mide/doxorubicin/fluorouracil [CAF])despite higher risk of recurrence. Thischemotherapy regimen is more “mod-ern” than the regimen of cyclophos-phamide/methotrexate/fluor ouracilused in earlier adjuvant studies. Theresearchers determined the RS for 367specimens and found that the RS wasprognostic for the group treated withtamoxifen alone. They also determinedthat CAF therapy had no benefit inpatients with a low RS, but that therewas an improvement in disease-free sur-vival (DFS) for women with a high RSafter adjustment for the number of pos-itive nodes. An improvement in breastcancer–specific survival (BCSS) wasalso observed for women with a highRS treated with chemotherapy. The10-year BCSS was 73% compared with54% for the tamoxifen alone group inthe high RS group. The predictivebenefit of the RS was significant in thefirst 5 years only (P = .029); there wasno additional prediction beyond thistime (P = .58), although there was acumulative benefit at 10 years (P =.053). The researchers concluded thata low RS identifies women who,despite positive nodes, might not ben-efit from CAF.9Based on these results, the Centers

for Medicare & Medicaid Services(CMS) extended coverage for OncotypeDX to ER-positive patients with micro -metastases and one to three positivenodes.10 An editorial in Lancet Oncologystates, “…the consistency across studiessuggests that there is little risk of falselyconcluding that there is no chemother-apy benefit in patients with low re cur-rence scores.”11Small studies have been conducted to

determine whether the 21-gene assaymay help predict response to neoadju-vant therapy. Anderson and colleagues

Multigene Signature Scores and Breast Cancer... Continued from cover

Dis

tan

t R

ecu

rren

ce a

t 10

Yea

rs

Recurrence Score

Low-Risk GroupIntermediate-

Risk Group High-Risk Group

Figure 1. Statistical link between recurrence score and distant breast cancer recurrence

Source: Reference 2. Reprinted with permission

from Genomic Health.

High,RS ≥31

0 10% 20% 30% 40% Absolute Increase (%) in DRFS at 10 Years (mean ± SE) from Chemotherapy

Low,RS <18

n = 134

n = 353

n = 164

DRFS indicates distant recurrence-free survival; RS, recurrence score; SE, standard error.

Figure 2. Statistical link between RS and the degree of response to chemotherapy

The researchers suggested that patients with a low RS might be candidates for a shorter course ofchemotherapy.

Source: Reference 3.Reprinted with permission

from Genomic Health.



Genetic Testing

compared RS, ER, PR, and HER2 scoresfrom core biopsies to surgical specimenson more than 11,000 samples. They hada 92% correlative success rate.12 Withthe confidence that core biopsies pro-vide accurate information, three smallstudies examined RS and response toneoadjuvant therapy.13-15 Two studiesused chemotherapy; one used hormonaltherapy. No patients with a low RS hada pathologic complete response (pCR)in the chemotherapy studies; however,these patients had a much better clinicalresponse in the hormonal therapy group.Therefore, assay results may help physi-cians and patients assess the benefit ofneoadjuvant therapy options.Finally, the usefulness of the 21-gene

assay for both physicians and patients hasbeen confirmed in several studies. Basedon assay results in node-negative pa -tients, physicians have reported changingtheir treatment recommendations 20%to 31.5% of the time. The most frequentchange is to omit chemotherapy.16-18 Atone comprehensive cancer center, thenumber of patients getting chemotherapydecreased from 55% to 25%.19 More than80% of patients stated that the resultsinfluenced their decisions, and more than90% were glad they took the test.Patients reported less anxiety and situa-tional conflict.20 Oratz and colleaguespolled more than 1000 physicians whoordered the assay for node-positivepatients and found that there was achange in chemotherapy recommenda-tion 42% of the time.21

70-gene prognostic signatureAvailable in Europe since 2004,

MammaPrint received US Food andDrug Administration (FDA) approval inFebruary 2007. It was the first clearanceissued by the FDA for a breast cancerrecurrence test based on data thatshowed that the gene signature addsindependent prognostic information toclinicopathologic risk assessment. Thetest was validated for use in patients lessthan 61 years of age with stage I or II,node-negative, ER-positive or ER-nega-tive tumors. MammaPrint was developedin an untreated, heterogeneous patientpopulation.22 In June 2007, Agendiaalso obtained FDA clearance for use ofits tissue preservative (RNARetain). Itshould be noted that there is a differ-ence in FDA approval and FDA clear-ance. Clearance provides marketingpermission for a test that is consideredto pose a low risk to public health andthat has been shown to be substantiallyequivalent to another test. Formalapproval provides marketing permis-sion for a test that is new or may be ofhigher risk to the user; studies are eval-uated that show the test does what itclaims. This 70-gene prognostic signa-ture became commercially available inthe United States in 2008.Using a process called microarray

gene chip technology, the test identi-fied 70 genes linked to the genomicpathways associated with breast cancerrecurrence. An algorithm was used toestablish two gene signatures (Figure 4,page 14). The test uses fresh-frozen tis-sue or tissue that must be put into aDNA preservative within an hour andthen mailed to the manufacturer. It doesnot provide an individual RS, but rather

binary results. A “low-risk signature” or“good prognosis” means a woman has a95% chance of DFS at 5 years, a 90%chance at 10 years, and a 99% BCSS rate at 5 years. A “high-risk signature” or“poor prognosis” means a woman has a78% chance of DFS at 5 years, a 71%chance at 10 years, and an 80% BCSSrate at 5 years.22-24The 70-gene prognostic signature has

been found to be of benefit in decidingprognosis in women with node-positivedisease. In 2007, Mook and colleaguespresented the results from 106 patientswith one to three positive lymph nodes.25They found that the 70-gene signatureoutperformed clinicopathologic prognos-tic factors. In patients with a good prog-nostic score, at 10 years, overall survival

There is A place you can go for user-friendly online tools and reimbursement forms…

…where your coverage questions can be Answered

…where online Access to forms is simple

…where you can talk to A single Amgen Reimbursement Counselor for all your reimbursement activity

For insurance verifi cation…prior authorization…patient assistance program information…billing and claims processing support…and appeals support.

Making Access easier.

with dedicated Amgen Reimbursement Counselors

Amgen Assist™ and Amgen Inc. do not guarantee success in obtaining reimbursement. Third party payment for medical products and services is affected by numerous factors, not all of which can be anticipated or resolved by our Amgen Assist™ staff.©Amgen. All rights reserved. MC48319-B 06/10

www.AmgenAssistOnline.com1-888-4ASSIST (1-888-427-7478)




Genetic Testing

(OS) was 99.7% and DFS was 94%. Inpatients with a poor prognostic score, OSwas 66% and DFS was 62%. Based onthese results, patients with one to threepositive nodes were incorporated into theMicroarray in Node Negative and 1 to 3 Positive Lymph Node Disease MayAvoid Chemotherapy (MINDACT) trialto obtain prospective validation.25 MIN-DACT is a prospective, randomized trialbeing conducted by an internationalbreast group (TRANSBIG) comparingthe 70-gene signature with the com-mon clinicopathologic criteria inselecting breast cancer patients withzero to three positive nodes for adju-vant chemotherapy.26

In addition, in 2009, Saghatchian andcolleagues reported an analysis of frozentumor samples from 519 node-positivepatients followed for 10 years. Theyfound the 70-gene signature to be astrong prognostic marker of diseaserecurrence and BCSS. Patients with ahigh genomic risk and elevated numberof positive lymph nodes (more thanthree) have a very poor prognosis; there-fore, the researchers suggested that thesepatients may want to consider moreaggressive treatment.27 Based on these

results, CMS provides coverage for the70-gene prognostic signature for allpatients with stage I and II breast cancer,including those with one to three posi-tive nodes.10

CMS coverage for the 70-gene signa-ture has also been expanded to includeall age groups. Bedard and colleagueslooked at 204 women aged 65 years andolder (median, 70 years). They foundthat the 70-gene signature remained anindependent prognostic indicator inthis group.28 Data were confirmed in agroup of patients between 55 and 70years of age.29

Finally, studies have been reportedshowing the predictive value of the 70-gene signature. Although there has beenno prospective analysis of the predictivevalue of this test in randomized, con-trolled, phase 3 trials, Knauer and col-leagues presented data at the 2009 St.Gallen Breast Cancer Conference on ameta-analysis of 1637 tumor samples ofwomen who received adjuvant chemo -therapy plus hormonal therapy or hor-monal therapy alone for T1-3, N0-1, M0breast cancers. This was a heterogeneousgroup of women: ER-positive, ER-nega-tive, HER2-positive, and HER2-nega-

tive. Median follow-up was 7.1 years.Data on 167 neoadjuvant chemotherapypatients were also reviewed. The re -searchers found that the 70-gene prog-nostic signature was predictive of neoad-juvant and adjuvant therapy. For low-riskpatients, chemotherapy plus hormonaltherapy did not demonstrate a signifi-cant benefit compared with hormonaltherapy alone; however, there was aclear benefit in high-risk patients. Inpatients who received neoadjuvanttherapy, there was no pCR in low-riskpatients, but there was a 20% pCR inhigh-risk patients.24,30,31

Agendia can also provide gene-expression levels of the ER, PR, andHER2 in freshly preserved tumor biop-sies using a high-density microchip assaycalled TargetPrint. TargetPrint has beenvalidated against FDA-approved IHCassays. It can be ordered with or withoutordering MammaPrint.

ConclusionThe additional information about the

clinical behavior of a patient’s cancerprovided by these assays should help theclinician in personalizing a therapeuticprogram for patients. Hopefully, fewerpatients who will not benefit fromchemotherapy will be exposed to thetoxicity of these agents. �

DisclosureMs Dell is a member of Genomic

Health’s speakers’ bureau.

References1. Edge S, Byrd DR, Compton CC, et al, eds. AJCCCancer Staging Handbook. 7th ed. New York, NY:Springer; 2010.2. Paik S, Shak S, Tang G, et al. A multigene assay topredict recurrence of tamoxifen-treated, node-negativebreast cancer. N Engl J Med. 2004;351:2817-2826.3. Paik S, Tang G, Shak S, et al. Gene expression andbenefit of chemotherapy in women with node-negative,estrogen receptor-positive breast cancer. J Clin Oncol.2006;24:3726-3734.4. Sparano JA. The TAILORx trial: individualizedoptions for treatment. Commun Oncol. 2006;3:494-496.5. Harris L, Fritsche H, Mennel R, et al; for theAmerican Society of Clinical Oncology. AmericanSociety of Clinical Oncology 2007 update of recommen-dations for the use of tumor markers in breast cancer. JClin Oncol. 2007;25:5287-5312.6. National Comprehensive Cancer Network. ClinicalPractice Guidelines in Oncology: Breast Cancer. V.2.2010.www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed March 26, 2010.7. Goldstein LJ, Gray R, Childset BH, et al. Prognosticutility of 21-gene assay in hormone receptor (HR) posi-tive operable breast cancer and 0-3 positive axillarynodes treated with adjuvant chemohormonal therapy(CHT): an analysis of Intergroup Trial E2197. J ClinOncol. 2007;25(18S):Abstract 526.8. Dowsett M, Allred C, Knox J, et al. Relationshipbetween quantitative estrogen and progesterone recep-tor expression and human epidermal growth factorreceptor (HER-2) status with recurrence in theArimidex, Tamoxifen, Alone or in Combination trial. JClin Oncol. 2008;26:1059-1065.9. Albain KS, Barlow WE, Shak S, et al; for the BreastCancer Intergroup of North America. Prognostic andpredictive value of the 21-gene recurrence score assay inpostmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a ret-rospective analysis of a randomised trial. Lancet Oncol.2010; 11:55-65.

10. Medicare Coverage Database. Baltimore, MD:Centers for Medicare & Medicaid Services; 2009.11. Andre F, Delalage S. First generation genomic testsfor breast cancer treatment. Lancet Oncol. 2010;11:6-7.12. Anderson JM, Shak S, Millward C, et al; for GenomicHealth Inc. Molecular characterization of breast cancercore biopsy specimens by gene expression analysis usingstandarized quantitative RT-PCR. San Antonio BreastCancer Symposium. 2009:Abstract 6021.13. Akashi-Tanaka S. Predicting responses to chemother-apy in breast cancer: from bench to bedside. Breast Cancer.September 30, 2009. Epub ahead of print.14. Gianni L, Zambetti M, Clark K, et al. Gene expres-sion profiles in paraffin-embedded core biopsy tissue pre-dict response to chemotherapy in women with locallyadvanced breast cancer. J Clin Oncol. 2005;23:7265-7277.15. Chang JC, Makris A, Gutierrez MC, et al. Geneexpression patterns in formalin-fixed paraffin-embeddedcore biopsies predict docetaxel chemosensitivity inbreast cancer patients. Breast Cancer Res Treat. 2008;108:233-240.16. Liang H, et al. A retrospective analysis of theimpact of Oncotype DX low recurrence score results ontreatment decisons in a single academic breast cancercenter. San Antonio Breast Cancer Symposium.2007:Abstract 2061.17. Lo SS, Norton J, Mumby PB, et al. Prospectivemulticenter study of the impact of the 21 gene recur-rence score (RS) assay on medical oncologist (MO)and patient (pt) adjuvant breast cancer (BC) treatmentselection. J Clin Oncol. 2007;25(18S):Abstract 577.18. Kamal AH, Loprinzi CL, Reynolds C, et al. Howwell do standard prognostic criteria predict OncotypeDX (ODX) scores? J Clin Oncol. 2007;25(18S):Abstract 576.19. Erb C, Fox KR, Patel M, et al. Evaluation of practicepatterns in the treatment of node-negative, hormone-receptor positive breast cancer patients with the use of theassay at the University of Pennsylvania. San AntonioBreast Cancer Symposium. 2007:Abstract 3082.20. Mumby PB, Lo SS, Norton J, et al. Prospectivemulti-center study of the impact of the 21-gene recur-rence score assay on patient satisfaction, anxiety anddecisional conflict for adjuvant breast cancer treatmentselection. San Antonio Breast Cancer Symposium.2007:Abstract 1092.21. Oratz R, Chao C, Skrzypczak S, et al; for GenomicHealth Inc. Effect of 21-gene recurrence score results ontreatment recommendations in patients with lymphnode-positive, estrogen receptor-positive breast cancer.San Antonio Breast Cancer Symposium. 2009: Abstract2031.22. Buyse M, Loi S, van’t Veer L, et al; for the TRANS-BIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negativebreast cancer. J Natl Cancer Inst. 2006;98:1183-1192.23. van’t Veer LJ, Dai H, van de Vijver MJ, He YD, etal. Gene expression profiling predicts clinical outcome ofbreast cancer. Nature. 2002;415:530-536.24. Straver M, Glas AM, Hannemann J, et al. The 70-gene signature as a response predictor for neoadjuvantchemotherapy in breast cancer. Breast Cancer Res Treat.2010;119:551-558.25. Mook S, Rutgers EJT, Peterse JL, et al. TheAmsterdam 70-gene signature predicts outcome in breastcancer patients with 1-3 positive lymph nodes. SanAntonio Breast Cancer Symposium. 2007:Abstract 1064.26. EORTC Trial 10041 (BIG 3-04)—MINDACT.October 14, 2009. www.eortc.be/services/unit/mindact/MINDACT_websiteii.asp. Accessed January 19, 2010.27. Saghatchian M, Mook S, Pruneri G, et al.Combining genomic profiling (70 gene-MamaPrint)with nodal status allows to classify patients with primarybreast cancer and positive lymph nodes (1-9) into verydistinct prognostic subgroups that could help tailor treat-ment. San Antonio Breast Cancer Symposium. 2009:Abstract 102.28. Bedard PL, Mook S, Knauer M, et al. The 70-geneprofile (MammaPrint) is an independent predictor ofbreast cancer specific survival for women 65 years of ageor older. San Antonio Breast Cancer Symposium.2009:Abstract 4049.29. Mook S, Schmidt MK, Weigelt B, et al. The 70-geneprognosis signature predicts early metastasis in breastcancer patients between 55 and 70 years of age. AnnOncol. October 13, 2009. Epub ahead of print.30. Knauer M, Staver M, Rutgers E, et al. The 70-geneMammaPrint signature is predictive for chemotherapybenefit in early breast cancer. Breast. 2009;18(suppl1):36. Abstract 73.31. Albain K, Paik S, van’t Veer L. Prediction of adju-vant chemotherapy benefit in endocrine responsive,early breast cancer using multigene assays. Breast.2009;18(S3):S141-S145.

Multigene Signature Scores and Breast Cancer... Continued from page 13

4+positive nodes

1-3positive nodes

Nodenegative

CI

Figure 3. Risk of distant recurrence increases with the number of positive nodes for all recur-rence scores

Threshold set with 10% false negatives(91% sensitivity, 73% specificity)

Figure 4. 70-gene prognostic signature, supervised analysis

Source: Reference 8. Reprinted with permission from Genomic Health.

Source: Reference 23. Reprinted with permission from Agendia.

TON_December 2010_FINAL_TON 12/6/10 2:21 PM Page 14

PROVENGE® is the first FDA-approved autologous cellular immunotherapy—activating a patient’s own antigen-presenting cells to stimulate an immune response against prostate cancer.

• Extended median survival beyond 2 years—25.8 months compared with 21.7 months for patients in the control group (P=.032)

• Reduction in risk of death—22.5% (HR=0.775, 95% CI: 0.614, 0.979)

• Most common adverse events—Chills, fatigue, fever, back pain, nausea, joint ache, and headache

• Therapy complete in 3 cycles—3 infusions, at approximately 2-week intervals*

*Each infusion is preceded by a standard leukapheresis procedure. The dosing interval ranged from 1 to 15 weeks in controlled clinical trials.

INDICATION: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases.In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.The most common adverse events (incidence ≥15%) reported in the PROVENGE group are chills, fatigue, fever, back pain, nausea, joint ache, and headache.

Please see Brief Summary of full Prescribing Information on the next page.

www.PROVENGE.com

©2010 Dendreon Corporation. All rights reserved. November 2010. Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation. P-A-11.10-072.00

In the fight against asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer...

Extends Survival

Now Available—To learn more about getting access to PROVENGE, call Dendreon ON Call at 1-877-336-3736.



Cancer Complications

MILAN—Painful vertebral compres-sion fractures can be promptly andeffectively treated with balloon kypho-plasty, according to an international

study presented at the 35th EuropeanSociety for Medical Oncology Congress.The Cancer Patient Fracture Eval -

uation (CAFE) study was the first to ran-

domize cancer patients with vertebralcompression fractures to balloon kypho-plasty or standard nonsurgical treatment(controls). The results were reported by

Leonard Bastian, MD, of the KlinikumLeverkusen in Leverkusen, Germany.“We found that we can reduce pain

immediately in these patients,” Bastian

PROVENGE® (sipuleucel-T)Suspension for Intravenous Infusion Rx Only

BRIEF SUMMARY — See full Prescribing Information for complete product information

INDICATIONS AND USAGE: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

DOSAGE AND ADMINISTRATION • For Autologous Use Only. • The recommended course of therapy for PROVENGE is 3 complete doses,

given at approximately 2-week intervals. • Premedicate patients with oral acetaminophen and an antihistamine such

as diphenhydramine. • Before infusion, confirm that the patient’s identity matches the patient identifiers

on the infusion bag. • Do Not Initiate Infusion of Expired Product. • Infuse PROVENGE intravenously over a period of approximately 60 minutes.

Do Not Use a Cell Filter. • Interrupt or slow infusion as necessary for acute infusion reactions, depending

on the severity of the reaction.

(See Dosage and Administration [2] of full Prescribing Information.)

CONTRAINDICATIONS: None.

WARNINGS AND PRECAUTIONS

• PROVENGE is intended solely for autologous use.

• Acute infusion reactions (reported within 1 day of infusion) included, but were not limited to, fever, chills, respiratory events (dyspnea, hypoxia, and bronchospasm), nausea, vomiting, fatigue, hypertension, and tachycardia. In controlled clinical trials, 71.2% of patients in the PROVENGE group developed an acute infusion reaction.

In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. The incidence of severe events was greater following the second infusion (2.1% vs 0.8% following the first infusion), and decreased to 1.3% following the third infusion. Some (1.2%) patients in the PROVENGE group were hospitalized within 1 day of infusion for management of acute infusion reactions. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, the infusion rate may be decreased, or the infusion stopped, depending on the severity of the reaction. Appropriate medical therapy should be administered as needed.

• Handling Precautions for Control of Infectious Disease. PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Universal precautions should be followed.

• Concomitant Chemotherapy or Immunosuppressive Therapy. Use of either chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. PROVENGE is designed to stimulate the immune system, and concurrent use of immunosuppressive agents may alter the efficacy and/or safety of PROVENGE. Therefore, patients should be carefully evaluated to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to treatment with PROVENGE.

• Product Safety Testing. PROVENGE is released for infusion based on the microbial and sterility results from several tests: microbial contamination determination by Gram stain, endotoxin content, and in-process sterility with a 2-day incubation to determine absence of microbial growth. The final (7-day incubation) sterility test results are not available at the time of infusion. If the sterility results become positive for microbial contamination after PROVENGE has been approved for infusion, Dendreon will notify the treating physician. Dendreon will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating physician. Dendreon may request additional information from the physician in order to determine the source of contamination.

(See Warnings and Precautions [5] of full Prescribing Information.)

ADVERSE REACTIONSBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety evaluation of PROVENGE is based on 601 prostate cancer patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in four

randomized, controlled clinical trials. The control was non-activated autologous peripheral blood mononuclear cells.

The most common adverse events, reported in patients in the PROVENGE group at a rate ≥15%, were chills, fatigue, fever, back pain, nausea, joint ache, and headache. Severe (Grade 3) and life-threatening (Grade 4) adverse events were reported in 23.6% and 4.0% of patients in the PROVENGE group compared with 25.1% and 3.3% of patients in the control group. Fatal (Grade 5) adverse events were reported in 3.3% of patients in the PROVENGE group compared with 3.6% of patients in the control group.

Serious adverse events were reported in 24.0% of patients in the PROVENGE group and 25.1% of patients in the control group. Serious adverse events in the PROVENGE group included acute infusion reactions (see Warnings and Precautions), cerebrovascular events, and single case reports of eosinophilia, rhabdomyolysis, myasthenia gravis, myositis, and tumor flare.

PROVENGE was discontinued in 1.5% of patients in Study 1 (PROVENGE group n=341; Control group n=171) due to adverse events. Some patients who required central venous catheters for treatment with PROVENGE developed infections, including sepsis. A small number of these patients discontinued treatment as a result. Monitoring for infectious sequelae in patients with central venous catheters is recommended.

Each dose of PROVENGE requires a standard leukapheresis procedure approximately 3 days prior to the infusion. Adverse events that were reported ≤1 day following a leukapheresis procedure in ≥5% of patients in controlled clinical trials included citrate toxicity (14.2%), oral paresthesia (12.6%), paresthesia (11.4%), and fatigue (8.3%).

Table 1 provides the frequency and severity of adverse events reported in ≥5% of patients in the PROVENGE group of randomized, controlled trials of men with prostate cancer. The population included 485 patients with metastatic castrate resistant prostate cancer and 116 patients with non-metastatic androgen dependent prostate cancer who were scheduled to receive 3 infusions of PROVENGE at approximately 2-week intervals. The population was age 40 to 91 years (median 70 years), and 90.6% of patients were Caucasian.

Table 1 Incidence of Adverse Events Occurring in ≥5% of Patients Randomized to PROVENGE

Any Adverse EventChillsFatigueFeverBack painNauseaJoint acheHeadacheCitrate toxicityParesthesiaVomitingAnemiaConstipationPainParesthesia oralPain in extremityDizzinessMuscle acheAstheniaDiarrheaInfluenza-like illnessMusculoskeletal painDyspneaEdema peripheralHot flushHematuriaMuscle spasms

591 (98.3)319 (53.1)247 (41.1)188 (31.3)178 (29.6)129 (21.5)118 (19.6)109 (18.1)

89 (14.8)85 (14.1)80 (13.3)75 (12.5)74 (12.3)74 (12.3)74 (12.3)73 (12.1)71 (11.8)71 (11.8)65 (10.8)60 (10.0)

58 (9.7)54 (9.0)52 (8.7)50 (8.3)49 (8.2)46 (7.7)46 (7.7)

186 (30.9)13 (2.2)

6 (1.0)6 (1.0)

18 (3.0)3 (0.5)

11 (1.8)4 (0.7)0 (0.0)1 (0.2)2 (0.3)

11 (1.8)1 (0.2)7 (1.2)0 (0.0)5 (0.8)2 (0.3)3 (0.5)6 (1.0)1 (0.2)0 (0.0)3 (0.5)

11 (1.8)1 (0.2)2 (0.3)6 (1.0)2 (0.3)

291 (96.0)33 (10.9)

105 (34.7)29 (9.6)

87 (28.7)45 (14.9)62 (20.5)

20 (6.6)43 (14.2)43 (14.2)

23 (7.6)34 (11.2)40 (13.2)

20 (6.6)43 (14.2)40 (13.2)34 (11.2)

17 (5.6)20 (6.6)

34 (11.2)11 (3.6)

31 (10.2)14 (4.6)

31 (10.2)29 (9.6)18 (5.9)17 (5.6)

97 (32.0)0 (0.0)4 (1.3)3 (1.0)9 (3.0)0 (0.0)5 (1.7)0 (0.0)0 (0.0)0 (0.0)0 (0.0)7 (2.3)3 (1.0)3 (1.0)0 (0.0)1 (0.3)0 (0.0)0 (0.0)2 (0.7)3 (1.0)0 (0.0)3 (1.0)3 (1.0)1 (0.3)1 (0.3)3 (1.0)0 (0.0)

All Gradesn (%)

All Gradesn (%)

Grade 3-5n (%)

Grade 3-5n (%)

PROVENGE (N = 601) Control* (N = 303)

(Table 1 continued on next page.)

Prompt Pain Relief for Vertebral Compression Fractures withBalloon KyphoplastyBy Caroline Helwick



Cancer Complications

said at a press conference. “Cancerpatients with vertebral compressionfractures having balloon kyphoplastyhave a superior outcome.”Balloon kyphoplasty involves a 1-cm

incision into the fractured vertebrathrough which a balloon is inserted andinflated to restore the shape and heightof the vertebra. The balloon is then

deflated and removed, and quick-set-ting bone cement is injected into thevertebral body to maintain the shape.The study population included 134

patients with three or fewer vertebralcompression fractures who were ran-domized to kyphoplasty (n = 70) ornonsurgical management (n = 64),mainly physical therapy, analgesics,

and sometimes braces and bed rest.Patients were followed for 1 year.After 1 month, the Roland-Morris

Disability Questionnaire score droppedby 8.3 points in the kyphoplasty groupbut increased slightly by 0.1 point inthe nonsurgical group. After just 1week, the kyphoplasty group reportedsignificant improvements in back pain,

with a change in the numerical ratingscale of -3.8 points, compared with vir-tually no change in the control group,and they used less analgesia.The difference between the groups in

the two pain measurements was highlysignificant (P <.0001), Bastian noted.Patients receiving balloon kypho-

plasty reported significantly fewer dayswith limited activity—6.2 days fewerper 2 weeks (P <.0001)—and greaterimprovements in quality of life asmeasured by an eight-point advantagein the SF-36 score (P <.0001).Crossover to kyphoplasty was allowed

after 1 month, and the 38 patients whodid so experienced similar benefits withregard to back pain relief, activity level,and quality of life.“All the balloon kyphoplasty pa -

tients reported sustained improve-ments through out the 12-month periodof the study,” Bastian said.Adverse events were similar except for

the occurrence of one intraoperativenon–Q-wave myocardial infarction thatresolved in the kyphoplasty group and acement leakage to the disc and adjacentfracture 1 day later in another patient.The indication for this procedure is

virtually any painful vertebral com-pression fracture or multiple fractures.Bones that have been highly compro-mised due to metastases, however, maynot be amenable to kyphoplasty. �

Rx Only

B

T

g P

a B

o I

D I

o

A

In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3 a

f h

C

H

C

i

P

(

T

r

≥

3 days prior to the infusion. Adverse events that were reported ≤1 day following a l t

i T a s p

R

Cerebrovascular Events. In controlled clinical trials, cerebrovascular events, including hemorrhagic and ischemic strokes, were reported in 3.5% of patients in the PROVENGE group compared with 2.6% of patients in the control group.

(See Adverse Reactions [6] of full Prescribing Information.)

To report SUSPECTED ADVERSE REACTIONS, contact Dendreon Corporation at 1-877-336-3736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Table 1 Incidence of Adverse Events Occurring in ≥5% of Patients Randomized to PROVENGE

HypertensionAnorexiaBone painUpper respiratory tract infectionInsomniaMusculoskeletal chest painCoughNeck painWeight decreasedUrinary tract infectionRashSweatingTremor

45 (7.5)39 (6.5)38 (6.3)38 (6.3)

37 (6.2)36 (6.0)

35 (5.8)34 (5.7)34 (5.7)33 (5.5)31 (5.2)30 (5.0)30 (5.0)

3 (0.5)1 (0.2)4 (0.7)0 (0.0)

0 (0.0)2 (0.3)

0 (0.0)3 (0.5)2 (0.3)1 (0.2)0 (0.0)1 (0.2)0 (0.0)

14 (4.6)33 (10.9)

22 (7.3)18 (5.9)

22 (7.3)23 (7.6)

17 (5.6)14 (4.6)24 (7.9)18 (5.9)10 (3.3)

3 (1.0)9 (3.0)

0 (0.0)3 (1.0)3 (1.0)0 (0.0)

1 (0.3)2 (0.7)

0 (0.0)2 (0.7)1 (0.3)2 (0.7)0 (0.0)0 (0.0)0 (0.0)

All Gradesn (%)

All Gradesn (%)

Grade 3-5n (%)

Grade 3-5n (%)

PROVENGE (N = 601) Control* (N = 303)

*Control was non-activated autologous peripheral blood mononuclear cells.

©2010 Dendreon Corporation. All rights reserved. November 2010. Printed in the U.S.A. Dendreon, the Dendreon logo, and PROVENGE are registered trademarks of Dendreon Corporation.P-A-11.10-073.00

Dendreon Corporation 3005 First Avenue Seattle, Washington 98121

Trastuzumab for HER2-positiveMetastatic Stomach CancerThe US Food and Drug Ad -

ministration (FDA) has ap provedtrastuzumab (Herceptin, Roche) incombination with chemo therapy(cisplatin plus either capecitabineor 5-fluorouracil) for human epi-dermal growth factor receptortype 2 (HER2)-positive metastaticcancer of the stomach or gastro -esophageal junction in patientswho have not received prior med-icines for their metastatic disease.Approval was based on results of

a phase 3 study (ToGA), whichshowed that patients who receivedtrastuzumab plus chemotherapyhad improved overall survival(HR, 0.73; 95% CI, 0.60-0.91; P =.0038). Median overall survivalwas 13.5 months for patients oncombination therapy comparedwith 11 months for those onchemotherapy alone. An analysisbased on an additional year of fol-low-up showed the numbers to beslightly lower (HR, 0.80; 95% CI,0.67-0.97; P = .02; median overallsurvival, 13.1 vs 11.7 months).

Recent FDAApproval



Cancer Center Profile

Geisinger’s Cancer Institute, believesthat serving this mix of patients marrieswell with the NCCCP’s mission ofreducing cancer healthcare disparities.NCCCP cancer centers are directed toincrease programs to reach the under-served in their communities more effec-tively, thus improving access to cancerscreening, treatment, and research.

Community outreachThe centerpiece at Geisinger is

value-based healthcare delivery, a phi-losophy evident in its advanced patient-centered medical home program,known as ProvenHealth Nav igator. AtGeis inger, medical homes are care-givers, such as primary care physiciansor nurse case managers, who provideservice excellence beyond just seeingpatients in an acute-care setting. Theirproactive approach to chronic diseasesis recognized by the National Com mitteefor Quality Assurance—all 40 facilitiesdistributed throughout Geisinger’s com-munity have been recognized as Level 3,the highest level awarded for the med-ical home model.This philosophy of managing patients

through a disease continuum that iscontinued into wellness programs—aphilosophy that is also practiced byGeisinger’s cancer specialists—parallelsthe NCCCP’s vision of cancer as a dis-ease continuum, according to Ravikumar.NCCCP cancer centers are tasked withimproving the quality of care at com-munity hospitals by promoting data-driven, evidence-based, and coordinat-ed cancer care. In addition, NCCCPcancer centers are working to enhancetheir cancer survivorship and palliativecare services. With a $1.7-million award from the

NCCCP, Geisinger hopes to reach thesegoals. To do so, Geisinger will use its

medical home model to reach patientsand physicians who are not members ofthe Geisinger system. “We need to pro-vide the same services to both Geisingerpatients and non-Geisinger patients inthe 11 counties that surround us,” saidRavikumar in an interview with TheOncology Nurse. “Our plan through theNCCCP, our obligation, is to allpatients in the counties that we serve.”

According to Ravikumar, Geisingerplans to reach out to area physicianswho are not participants in the Geis -inger system through the KeystoneHealth Information Exchange (KeyHIE)initiative. This initiative aims to pro-vide healthcare professionals with thetimely information they need to providethe best care possible for their patients.Through the initiative’s master patientlist, patients’ charts and all medicalinformation that reside at any partici-pating hospital can be accessed througha secure web-based browser.

Information technologyGMC’s Cancer Institute also has “sig-

nificant strength in information tech-nology,” noted Ravikumar. This isanother area that marries well with theNCCCP’s mission. NCCCP cancercenters are charged with exploring whatis needed to adapt or adopt the tools ofthe National Cancer Institute’s (NCI)

cancer Bioinformatics Grid (caBIG) aswell as to enhance their electronichealth record (EHR) networks to sup-port and link cancer patients andresearchers nationwide. “What theNCCCP wants to do is connect all thecancer centers in the country through agrid called caBIG. They are trying tobring everyone up to speed. We arealready advanced in that area, so per-haps the NCCCP thought that it wouldbe a good thing for centers like ours tolead the way,” said Ravikumar. For the past 8 years, Geisinger has

been recognized as one of the nation’s“100 Most Wired Hospitals and HealthSystems” by Hospitals & HealthNetworks (H&HN), the journal of theAmerican Hospital Association. As oneof the most digitally advanced health-care providers in the nation, Geisingeruses information technology to addresssafety and quality, customer service,business processes, workforce, and pub-lic health.

ResearchIn addition, Geisinger already has a

very robust biospecimen initiativethrough MyCode. Currently, MyCodehas 20,000 DNA samples from patientsthroughout Geisinger. Patients at all lev-els of health are asked to participate, pro-vide a blood sample, and give consent forits use in research. “If any studies need tobe done across the cancer research at thecommunity level, we are well positionedto carry out the mission of the NCCCP,”explained Ravikumar. To help theNCCCP reach its goal of applying NCIBest Practices for Biospecimen Re sourcesto enable all community cancer centersto contribute to the national biobank,Geisinger is expanding its specimen col-lection beyond Geisinger-affiliated can-cer centers by “helping them retrieve thespecimen when they operate on cancerpatients,” Ravikumar said.As a member of the Community

Clinical Oncology Program (CCOP),Geisinger already has 11 of the 15NCCCP clinical trials open at its can-cer centers. According to Ravikumar,Geisinger plans to expand those 11 tri-als and open the additional four trials topatients in its community. Because of itsrural patient base, Geisinger will offertrials at multiple sites so, as Ravikumarexplains, the patients “do not have tocome to us in our main center.” In addi-tion, Geisinger accrues to trials throughother oncology groups including theEastern Cooperative Oncology Groupand the North Central Cancer Treat -ment Group. “Using the NCCCPmechanism, we are going to make thesetrials available to people in the commu-nity through outreach and navigatorsand transportation service,” explained

Ravikumar. “In addition, for clinical tri-als, we are going to enlist oncologists,radiation doctors, surgeons, and primarycare physicians who are not Geisingerphysicians and make sure that theyhave access to NCCCP clinical trials.”

Quality careAll of this, of course, is about the qual-

ity of care delivered. “We have someideas of how we will use our EHR and ourmodel of ProvenHealth to improve thequality of patient care, so every patientgets the same level of care,” saidRavikumar, a surgeon by profession. Thiscare will continue through the diseasecontinuum and include survivorship andpalliative care. This past year, Geisingerhas launched the Geisinger acceleratedperformance program (GAPP) initia-tive. “One of the central focuses of theGAPP initiative is palliative care, mak-ing sure that the patients that we can-not cure we offer palliation as a focusand that we keep their quality of lifecentral to our mission.” GMC’s Cancer Institute will not be

resting on its laurels. By becoming anNCCCP cancer center, Geisingerhopes to improve on its delivery of in -novation and discovery and to enhanceits diffusion of research and technologyto positively influence cancer caretoday and tomorrow. Ravikumar looksforward to working with the otherphysician directors at the other sites.“We belong to the club. We may haveone model. Others may other models.We will basically learn from eachother,” Ravikumar said. �

Geisinger Medical Center’s Cancer Institute Joins the NCCCP Continued from cover

Thanjavur Ravikumar, MD, FACS, performs surgery in Geisinger’s Center forSurgical Innovation.

The centerpiece atGeisinger is value-basedhealthcare delivery, aphilosophy evident in itsadvanced patient-centered medical homeprogram.

Dasatinib for Ph+ CP-CMLThe US Food and Drug Admin -

istration (FDA) has ap proved a newindication for dasatinib (Sprycel,Bristol-Myers Squibb)—treatmentof Philadel phia chromosome–posi-tive chronic phase chronic myeloidleukemia (Ph+ CP-CML). Thisindication ex pands on the drug’soriginal approval in 2006 to treatadults with CP-CML with resistantdisease or who were intolerant ofprior therapies.An oral kinase inhibitor, dasa-

tinib’s side effects can include de - creased bone marrow activity, fluidretention, diarrhea, head ache, mus-cle and bone pain, and rash.Because it was approved under theFDA’s accelerated approval pro-gram, the manufacturer is requiredto collect additional long-term effi-cacy and safety data.

Recent FDAApproval


STARTS STRONG. LASTS LONG.

IndicationALOXI® (palonosetron HCl) injection 0.25 mg is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy.

Important Safety Information

of its components

include headache (9%) and constipation (5%)

Please see the brief summary of the Full Prescribing Information on the adjacent page.

References: 1. Gralla R, Lichinitser M, Van der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577. 2. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003;98:2473-2482. 3. Data on fi le. Eisai Inc., Woodcliff Lake, NJ. 4. Aapro MS, Grunberg SM, Manikhas GM, et al. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol. 2006;17:1441-1449.

ALOXI®

Help support your patients’ chemotherapy treatment goals Powerful CINV prevention in the fi rst 24 hours and up to 5 days following

moderately emetogenic chemotherapy1,2

Lasts long against nausea following moderately emetogenic chemotherapy

Powerful acute CINV prevention following highly emetogenic chemotherapy4

ALOXI® provides powerful CINV prevention that can’t be ignored.



Lung Cancer

SAN DIEGO—Stereotactic radiationappears to be highly effective and safe fortreatment of patients with operable,

early-stage non–small-cell lung cancer(NSCLC). In some cases, it may be anappropriate alternative surgery, resulting

in fewer side effects, according to anew Japanese study presented at the52nd annual meeting of the American

Society for Radiation Oncology.Stereotactic body radiation therapy

(SBRT) is an increasingly popular treat-ment and has been shown to be effectivein medically inoperable stage I NSCLCpatients. This trial, however, was the firstto examine its use in stage I lung cancerpatients who are eligible for surgery.“We can now confirm with more

confidence that SBRT is an effectivetreatment alternative for [older] agedpatients with non–small-cell lung can-cer,” said Yasushi Nagata, MD, a profes-sor of radiation oncology at HiroshimaUniversity, Japan. “In the future, thereis a possibility that radiation will be asubstitute for surgery in selectedpatients with stage I NSCLC. I encour-age patients with early lung cancer totalk to their doctor to understand alltheir treatment options.”In this study, patients underwent four

radiation treatments over the course of 4to 8 days. SBRT, sometimes called radio-surgery, refers to a single or several high-ly targeted radiation treatments.From July 2004 to January 2007, 65

patients from 15 institutions were fol-lowed for a median of 45 months post-treatment. Researchers sought to deter-mine the effectiveness and safety ofstereotactic radiation treatments bydetermining the patient group’s overallsurvival at 3 years after treatment (76%).The mean age of the patients was 79years (range, 50-91 years), and 45 of 65patients were men. The median tumorsize was 21 mm (range, 10-30 mm).To date, a total of 25 progressions have

been observed, and the 3-year progres-sion-free survival rate is 54.5%. Thelocal progression-free survival rate at 3years is 68.5%, and the event-free sur-vival rate is 51.4%. No grade 4 or 5 tox-icities have been observed. Grade 3adverse events included chest pain in1.5%, dyspnea in 3.1%, hypoxia in 1.5%,and pneumonitis in 3.1%.“This would be a lot less painful than

surgery,” said Nagata in an interviewwith The Oncology Nurse. “There is alsoa big cost savings. The cost could be halfof surgery. This is something thatAmerican cancer specialists may want tothink about. It is important for theoncology nurse to know about this too.This could be a substitute for surgery, andpatients need to know this.”He said this study is particularly

important because it included so manyolder-aged patients. Nagata said that inthe United States this approach for thesepatients is only now starting to becomepart of clinical practice. �

ALOXI® (palonosetron HCl) injection

BRIEF SUMMARY OF PRESCRIBING INFORMATION

INDICATIONS AND USAGE

Chemotherapy-Induced Nausea and VomitingALOXI is indicated for:

DOSAGE AND ADMINISTRATIONRecommended DosingChemotherapy-Induced Nausea and Vomiting

Instructions for I.V. Administration

CONTRAINDICATIONS

[see Adverse Reactions (6) ]

WARNINGS AND PRECAUTIONSHypersensitivity

ADVERSE REACTIONS

≥

Table 1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies ≥ 2% in any Treatment Group

Postmarketing Experience

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONSPregnancy

Labor and Delivery

Nursing Mothers

Pediatric Use

Geriatric Use

≥

≥ ≥

≥

Renal Impairment

Hepatic Impairment

Race

OVERDOSAGE

PATIENT COUNSELING INFORMATION FDA-Approved Patient Labeling (17.2) in

Instructions for Patients

see Adverse Reactions (6)

ALOXI®

EventALOXI

0.25 mg (N=633)

Ondansetron 32 mg I.V. (N=410)

Dolasetron 100 mg I.V.

(N=194)

Stereotactic Radiation May Be as Effective as Surgeryfor Some Non–small-cell Lung CancersBy John Schieszer

See also pages 25 & 32.


Nominate a Nurse online atwww.TheOncologyNurse.com/award

Who Will Be theONE?The OncologyNurse ExcellenceAward Winner

The Oncology Nurse-APN/PA is pleased to

announce the inaugural Nurse Excellence

Award. The award will recognize an

oncology nurse nominated by his/her

peers for an outstanding contribution to

oncology nursing practice, patient care,

research, or education in 2010.

The four leading nominees will be profiled

in the February issue of The Oncology

Nurse-APN/PA. Readers will have an

opportunity to vote for the winner online

at www.TheOncologyNurse.com/award or

by visiting The Oncology Nurse-APN/PA

booth at the 2011 ONS Congress. The

winner will be announced in the June

issue of The Oncology Nurse-APN/PA .

�� TON_December 2010_FINAL_TON 12/6/10 11:20 AM Page 21

Supportive care: The most common initial MDS treatment90% of patients with newly diagnosed myelodysplastic syndromes (MDS) present with anemia, and most patients eventually become red blood cell (RBC) transfusion dependent.1 For years, MDS was treated with best supportive care—RBC or platelet transfusions and antibiotics.2 With the advent of hematopoietic growth factor therapy, supportive care expanded to include erythropoiesis-stimulating agents (ESAs), with or without G-CSF,† which were used to reduce the need for transfusions.3,4

Survival decreases with increasing transfusion requirements5

Therefore, it is critical to achieve transfusion independence in patients with transfusion- dependent MDS. While ESAs can effectively relieve the symptoms of anemia, they may not be sufficient to provide RBC transfusion independence in all MDS patients.6-9 Some of your patients with lower-risk MDS may need treatment other than growth factors (GFs).

Use baseline serum erythropoietin (sEPO) levels to guide treatment decisionsBecause the response to ESAs declines with increasing baseline sEPO levels, it is critical to measure endogenous levels of erythropoietin before initiating treatment with ESAs. As many as 85% of patients with MDS have elevated baseline sEPO levels,10 making them less likely to respond to growth factors. Patients with high sEPO levels (>500 U/L) and high transfusion needs (≥2 RBC units/month) have a low chance of response to erythropoietin.3 Current treatment guidelines recommend that the determination of baseline sEPO levels should be a required part of the initial evaluation of patients with cytopenias.11

©2010 Celgene Corporation 07/10 CELG10174T

* MDS, myelodysplastic syndromes; lower-risk MDS, Low- and Intermediate-1–risk MDS per International Prognostic Scoring System (IPSS).

† G-CSF, granulocyte colony-stimulating factor. Growth factor therapy includes ESA ± G-CSF or granulocyte/macrophage (GM)-CSF.3

Clinical challenge: Treatment selection for patients with lower-risk MDS*


CELG10174T

*

23%Chance of

responding to ESAs‡

74% 7%

References: 1. Italian Cooperative Study Group For rHuEpo in Myelodysplastic Syndromes. A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br J Haematol. 1998;103:1070-1074. 2. Nimer SD. ASH 50th anniversary review: Myelodysplastic syndromes. Blood. 2008;111(10):4841-4851. 3. Sekeres MA, Fu AZ, Maciejewski JP, Golshayan A-R, Kalaycio ME, Kattan MW. A decision analysis to determine the appropriate treatment for low-risk myelodysplastic syndromes. Cancer. 2007;109(6):1125-1132. 4. Fenaux P, Kelaidi C. Treatment of the 5q- syndrome. American Society of Hematology Education Program–Myelodysplastic Syndromes. Hematology. 2006;192-198. 5. Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica. 2006;91(12):1588-1590. 6. Jädersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellström-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106(3):803-811. 7. Miller KB, Kim HT, Greenberg P, et al. Phase III prospective randomized trial of EPO with or without G-CSF versus supportive therapy alone in the treatment of myelodysplastic syndromes (MDS): results of the ECOG-CLSG trial (E1996). Blood. 2004;104(11):24a. Abstract 70. 8. Musto P, Lanza F, Balleari E, et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2004;128(2):204-209. 9. Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6):1037-1046. 10. Hofmann W-K, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med. 2005;56:1-16. 11. National Comprehensive Cancer Network®. Myelodysplastic Syndromes. V.2.2010. NCCN Clinical Practice Guidelines in Oncology ™.

If your patients have a predicted intermediate or poor response to ESAs, it may be appropriate to consider non-growth factor therapies.3

‡ The Hellström-Lindberg study defined complete erythroid response as an increase in hemoglobin (HgB) to ≥11.5 g/dL. Partial response was defined as an increase in HgB of ≥1.5 g/dL in patients with anemia who are not transfusion dependent, and for RBC transfusion-dependent patients, a stable HgB level for ≥4 weeks and transfusion independence.9

Consider baseline sEPO levels and transfusion burden when determining treatment options for your RBC transfusion-dependent patients with lower-risk MDS. It is also important to continually evaluate these patients.

Low (<2 units/month)

Low (≤500 U/L)

High (≥2 units/month)

Low (≤500 U/L)

High (≥2 units/month)

High (>500 U/L)

Two variables can be used to help predict response to growth factor therapy: Baseline sEPO levels and RBC transfusion burden9

Low (<2 units/month)

High (>500 U/L)

POORINTERMEDIATEGOOD

sEPO Level

Transfusion Requirement

Adapted from Hellström-Lindberg et al (2003).9



International News

Increased Cancer Risk inInsulin Users Decreases Over TimeSTOCKHOLM—New data underminethe widely held notion that thegreater likelihood of cancer seen indiabetic patients on insulin therapyincreases with longer insulin use.In fact, the findings, reported at the

46th European Association for theStudy of Diabetes meeting, show thatthe increased cancer risk in diabetesdrops substantially with long-terminsulin use.Daniel Witte, MD, PhD, research

group leader at the Steno DiabetesCenter in Gentofte, Denmark, andcolleagues tracked the entire Danishpopulation of 5.5 million people over13 years to assess the associationbetween length of insulin use andcancer incidence. The Steno DiabetesCenter is owned by Novo Nordisk.Over the past several decades,

numerous studies have found elevatedrates of cancer of the liver, kidney,

female breast, and corpus uteri in dia-betic patients.The new study confirmed that there

is an excess cancer risk in patientswith diabetes and also that insulin-using diabetics have a higher cancerrisk than diabetics not using insulin.For example, 20.9% of nondiabeticDanish men 65 years of age and olderare likely to develop cancer over thenext 10 years compared with 22.3% ofdiabetic men not using insulin and23.7% of diabetic men using insulin.The corresponding figures for womenare 15.4%, 16.1%, and 19.5%.For all cancer types combined, the

effect of insulin use was highestimmediately after the start of treat-ment and decreased to a stable level 3to 4 years after the first insulin pre-scription. This pattern was also seenfor the duration of diabetes, with therisk being highest in the period justafter diagnosis and decreasing to apoint where the patient had no excessrisk after 3 years.

The investigators say that theirs isthe largest registry linkage study todate to focus on diabetes.The investigators noted that their

results suggest that it may not beduration or insulin that carries therisk. Instead the risk may be partlydue to causes common to cancer anddiabetes/insulin treatment, such asobesity.

Thyroid Cancer PatientsEmbrace UnconventionalTreatmentsPARIS—Most patients with thyroid can-cer report that they used some form ofcomplementary and alternative medicine(CAM) over the past 12 months, re -searchers reported at the 14th In -ternational Thyroid Congress.Jennifer E. Rosen, MD, assistant pro-

fessor of surgery at Boston UniversitySchool of Medicine, Massachusetts, andcolleagues analyzed responses to anonline questionnaire on CAM use thatwas completed by 1324 patients whobelonged to a thyroid cancer survivors’organization.The survey found that 80% of patients

said they had used some form of CAMtherapy during the past 12 months andthat only 6.6% of respondents said thatthey did not use any form of CAM.The two most commonly used CAM

therapies were prayer (35.3%) and multi-vitamins (41.8%). When prayer and mul-tivitamins were excluded from the analy-sis, 67.5% of patients used some form ofCAM therapy during the past 12 months.After prayer and multivitamins, the fivemost commonly used CAM practicetherapies were massage therapy, chiro-practic therapy, yoga, meditation, andacupuncture. The five most commonlyused CAM biologic therapies were herbaltea, special diets, herbal supplements,homeopathy, and ginger.CAM therapies were most often

used for the treatment of symptoms(69.1%), but a high percentage ofpatients used CAM as part of theirthyroid cancer treatment (30.9%).More than half of patients (54.2%)said that they had used CAM morethan 10 times in the past 12 months.About two thirds of patients believed

that CAM treatments were helpful, andabout one third believed that they had noeffect. Nearly 20% of respondents report-ed that their physician did not know thatthey were using CAM therapies and hadnot inquired about CAM use.

Overall, the results demonstratethat the rate of CAM use in thyroidcancer patients is twice that reportedfrom national surveys of the generalUS population.

Interactive Presentation HelpsInform Patients AwaitingCancer SurgeryMELBOURNE—Investigators at theUniversity of Melbourne are reportingfavorable results using an interactivemultimedia presentation (IMP) toteach prostate cancer patients sched-uled for a radical prostatectomy (RP)about their procedure and potentialcomplications.In fact, preliminary findings show

that patients who watched an IMPscored better on a knowledge test thanpatients who underwent the conven-tional surgery consent process.For the study, 40 men wait-listed for

open RP were randomized to eitherthe standard surgery consent processor IMP.With the standard consent process,

patients received detailed informationabout the procedure from physiciansand nurses.Patients assigned to the IMP group

watched 51 slides that described basicanatomy, how the prostate works, andhow the operation is performed andalso provided information on potentialcomplications and postoperative care.About half of the slides included inter-active questions that had to beanswered correctly before the patientcould view the next slide.Results showed that patients in the

IMP group answered 36% more ques-tions about the procedure correctly thanpatients in the standard consent group.In addition to improving patient

knowledge, the IMP can help medicalstaff obtain informed consent and alsoreduce patient anxiety and potentialdissatisfaction as well as the possibilityof a lawsuit if the surgery is not as suc-cessful as anticipated.Study investigator Nathan Lawrent -

schuk, MBBS, FRACS, a urologiconcologist, and his colleagues pointedout that although the IMP evaluated inthe study was developed for prostatecancer surgery, the tool can potentiallybe adapted for use in patients awaitingother surgical procedures. The investigators reported their

results in the October 2010 issue of theBritish Journal of Urology International. �

Reports from the European Association for the Study ofDiabetes, the International Thyroid Congress, and theUniversity of MelbourneBy Jill Stein

CARTOON



Lung Cancer

SAN DIEGO—Two studies presented atthe 52nd annual meeting of the Am -erican Society for Radiation Oncologyhave found that the use of fast neutronradiotherapy (FNRT), a form of radia-tion that is about three times more pow-erful than typical photon radiotherapy, ishighly effective and safe for patients withnon–small-cell lung cancer (NSCLC).Researchers analyzed results for

NSCLC patients who were treated at asingle institution from 1993 to 2006.Treatments included a combination offast neutron and photon radiotherapy.FNRT lost favor in the medical commu-nity in the past because, in some cancerpatients, delivering FNRT resulted inhigher toxicities.

“There are only five centers in theworld that are using fast neutron thera-py,” said study investigator AndreKonski, MD, MBA, who is professor andchair of the Department of RadiationOncology at Wayne State UniversitySchool of Medicine, Detroit, Michigan.“It is able to treat tumors that are resis -tant to photon radiotherapy.”Konski said 20% to 30% of lung can-

cer patients do not respond to photonradiotherapy and still have significantsymptoms. “They still need to have theirsymptoms palliated, and we are able topalliate their symptoms,” he said in aninterview with The Oncology Nurse. “Ourfindings are good news, and we werehappy that we did not have similar toxi-cities as have been seen in treating simi-lar patients.”Although FNRT can help with many

types of cancer, it reportedly works beston lung cancer, sarcomas, glioblastomas,prostate cancer, and head and neck can-cers. In the FNRT study for salvage ther-apy, Konski and his colleagues studiedthe outcomes of 20 patients withNSCLC who had failed primary treat-ment with chemotherapy and/or radio-therapy. The estimated clinical relative

biological effectiveness for neutronradiotherapy was found to be three timesgreater than photon radiotherapy in thenormal lung tissue and four times more

effective for targeted tumors. In thestudy group, there were no grade 3 or 4toxicities. All treatment-related toxic-ities, such as radiation pneumonitis,

esophagitis, and radiation dermatitis,were adequately treated on an outpa-tient basis.

Fast Neutron Radiotherapy May Be Safe and Effectivefor Lung Cancer PatientsBy John Schieszer

The estimated clinicalrelative biologicaleffectiveness for neutronradiotherapy was foundto be three timesgreater than photonradiotherapy in thenormal lung tissue.

You read it first in

www.TheOncologyNurse.com

Beforethe research is published…

Beforethe guideline is issued…

Beforethe drug is approved…

The addition of new biomarkers forestablishing a prognosis for pa -tients with breast cancer has beenrecommended in the 2010 edition of theAmerican Joint Committee of Cancer’sCancer Staging Handbook.1 Human epider-mal growth factor receptor type 2(HER2) status and multigene signature“scores” have been added to estrogenreceptor (ER) and progesterone receptor(PR) determinations.1 So, where are weregarding multigene signature scores? Atthis time, two tests are commercially

available in the United States: OncotypeDX (Genomic Health) and MammaPrint(Agendia).

21-gene recurrence score assayAvailable since 2004, Oncotype DXuses a process called reverse-transcriptasepolymerase chain reaction (RT-PCR) tolook at 21 genes: 16 are linked to breastcancer and five are reference genes usedfor normalizing the expression of the can-cer-related genes. The chosen genes have

DECEMBER 2010www.TheOncologyNurse.com

VOL 3, NO 8

Journal ofOncology Navigation &Survivorship™

between pages 34 and 35

Journal of Oncology

™The Official Journal of the Academy of Oncology Nurse Navigators


DECEMBER 2010

www.AONNonline.org

VOL 1, NO 7

Lillie Shockney, RN, BS, MASJohns Hopkins Breast CenterJohns Hopkins UniversitySchool of MedicineBaltimore, MarylandSharon Gentry, RN, MSN, AOCN,CBCNDerrick L. Davis ForsythRegional Cancer CenterWinston-Salem, North CarolinaNicole Messier, RNVermont Cancer CenterBurlington, Vermont

Pamela Matten, RN, BSN, OCNSt. Joseph HospitalOrange, CaliforniaElaine Sein, RN, BSN, OCN, CBCNFox Chase Cancer Center PartnersRockledge, Pennsylvania

Tricia Strusowski, MS, RNHelen F. Graham Cancer CenterChristiana Care Health SystemNewark, DelawareLinda Fleisher, MPH, PhD(c)Fox Chase Cancer CenterCheltenham, Pennsylvania


Jay R. Swanson, RN, BSN, OCNSaint Elizabeth Cancer InstituteLincoln, NebraskaCarol Lewis, RN, BSN, OCN, CRNIMemorial HermannThe Woodlands, Texas


Leadership Council


AONN Staff

www.AONNonline.org

GUIDE OUR PATHStart a Local, State, or Regional Affiliate,Join a Committee

The George Washington CancerInstitute (GWCI) recently re -ceived a $2.4 million grant fromthe DC Cancer Consortium to estab-lish and coordinate a City-wide PatientNavi gation Network (CPNN) inWash ington, DC. The CPNN will create a seamless,cohesive framework for coordination ofcancer care throughout the city to ensurethat all city residents get appropriate can-cer screening and treatment regardless oftheir ability to pay. The network will alsohelp patients identify support servicesthroughout the cancer continuum, in -cluding posttreatment survivorship. Twenty-five separate institutions,including hospitals, cancer centers, andcommunity organizations in theWashington, DC, area are members of





Continued on page 2

CARE COORDINATIONCity-wide Patient Navigation NetworkCoordinates Washington, DC, Cancer CareBy Karen Rosenberg

The Center for the Advancementof Cancer Survivorship, Navi -gation, and Policy (caSNP), acollaboration of the George Wash ingtonCancer Institute (GWCI) and the uni-versity’s School of Public Health andHealth Services Department of HealthPolicy, was established in 2009 with support from Pfizer and the PfizerFoundation. The center’s goals are toadvance patient navigation and cancersurvivorship efforts both locally andnationally through training, research,

policy analysis, and education. caSNP grew out of the understandingthat there is “overlap between patientnavigation, survivorship, and policy andboth of these intersect with local andnational healthcare policy,” explainedSteven Patierno, PhD, executive directorof the GWCI. “We wanted to create aplatform to talk about navigation and sur-vivorship in the context of policy in aunited program.” The center offers training programs atthree levels:

• Navigation training is designed fornavigators, including nurses, socialworkers, and lay persons. Traineesfrom institutions across the coun-try learn about barriers that affecttheir patients, are trained tolaunch or improve programs, andgain tools for implementing insti-tutional change.• Executive level training is de signedfor chief executive officers, chieffinancial officers, hospital adminis-

NAVIGATION TRAININGCenter Provides Platform for Discussion ofCancer Survivorship, Navigation, and Policy

By Karen Rosenberg

Continued on page 2

“The CPNN will create a seamless,cohesive framework for coordination ofcancer care throughout the city. ” —Steven Patierno, PhD

GENETIC TESTINGMultigene Signature Scores andBreast Cancer 2010By Deena Damsky Dell, MSN, RN-BC, AOCN Clinical Nurse Specialist, Fox Chase Cancer Center,Philadelphia


Fostering a Dialogue to Improve Patient Care & Outcomes

Submit your cases online today at www.myelomacases.com


Inside

Mammography technologist Jessica Davis, RT(R) (M), is part of a multi-

disciplinary breast cancer care team working to improve access to

screening, treatment, and research.

Geisinger Medical Center’sCancer Institute Joins theNCCCPBy Dawn Lagrosa

This past April, Geisinger Medical Center’s (GMC) Cancer In -

stitute became one of 14 sites added to the National Cancer

Institute Community Cancer Centers Program (NCCCP). Joining

this national network of community cancer centers offers GMC the

opportunity to expand its state-of-the-art cancer care and research in

northeast Pennsylvania.GMC is a part of Geisinger Health System (Geisinger), which serves

a mostly rural population and has cancer centers in Danville, Wilkes-

Barre, State College, and Hazleton. Geisinger takes pride in its innova-

tive approach to healthcare delivery to this population, which also

includes many elderly patients. In addition, a significant portion is

underserved because of socioeconomic status and transportation

problems. Thanjavur Ravikumar, MD, FACS, director of the Center for

Surgical Innovation, and co-chair of the oncology service line at

CANCER CENTER PROFILE


CONFERENCE NEWSOncology Nursing Society’s 11th AnnualAdvanced Practice Nursing Conference/Institutes of LearningOrlando, Florida, November 11-14, 2010.See who was there: page 8.

Kimberly Gessner, Holly Gentry, and Marlene Ferguson display copies of The Council of

Dads, a book by keynote speaker Bruce Feiler.Lung CancerStereotactic Radiation for Non–small-cell Lung CancersPage 20

Fast Neutron RadiotherapyPage 25

Continuing Education Maintenance "erapy in Patients withAdvanced Non–small-cell Lung CancerPage 30

Breast CancerProlonging Chemotherapy in MetastaticBreast Cancer Improves SurvivalPage 44




ONS APN/IOL

Telephone Support Increases Adherence to IV Chemotherapyfor Recurrent Ovarian CancerBy Fran Lowry

ORLANDO—Women who are onintravenous (IV) chemotherapy regi-mens for recurrent ovarian carcinomaare at risk for nonadherence or nonper-sistence with their treatment. But tele-phone support by an advanced practicenurse (APN) can lower this risk andeven boost compliance, a new, nonran-domized study suggests.

“Nonadherence is not just an issuewith oral chemotherapy,” said SusanMoore, RN, MSN, ANP, AOCN, ofMCG Oncology, Chicago, Illinois, at herposter presentation. “Patients who are onIV regimens can also be nonadherentwith their treatment. We think they areadherent because they show up, butoften they are nonpersistent, meaningthat they stop before the end of aplanned regimen. Telephone support isjust another way for APNs to do theiroutreach to patients.”

APNs are challenged to developprograms that support patient adher-ence and persistence to prescribedcancer therapies, especially therapiesfor advanced disease. Ovarian canceris a particularly difficult cancer totreat, Moore noted.

“Patients who are on liposomal dox-orubicin may not be completing theirfull six cycles. Many drop out becauseof side effects that are not well man-aged. Patients who are on this drughave usually been on other chemother-apies before, so they already know thedrill,” she said. “They’re not having avery good quality of life. Sometimespatients are afraid or embarrassed tocall their nurse or their doctor to tellthem they want to quit. Instead, they

just don’t come back.” This study evaluated the efficacy of

an APN-staffed telephone patient-sup-

port program in increasing adherence to IV chemotherapy in this setting.Participants in the program received a

telephone call from an oncology APNbefore and after each chemotherapyinfusion for up to six cycles to reinforce


Conference News

ISTODAX® is a registered trademark of Astellas Pharma, Inc.©2010 Celgene Corporation 10/10 IST10074

Please see following pages for Brief Summary of full Prescribing Information.

P

Important Safety InformationWARNINGS AND PRECAUTIONS:• Due to the risk of QT prolongation, ensure that

potassium and magnesium are within the normal range before administration

• Treatment with ISTODAX® has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with ISTODAX and modify the dose as necessary

• Electrocardiographic (ECG) changes have been observed with ISTODAX

• In patients with congenital long QT syndrome, a history of signifi cant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to signifi cant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment

• Based on its mechanism of action, ISTODAX may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D)

• ISTODAX binds to estrogen receptors. Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives

ADVERSE REACTIONS:The most common Grade 3/4 adverse reactions (>5%) regardless of causality reported in Study 1 (n=102) were infections (11%) and asthenia/fatigue (8%) and in Study 2 (n=83) were lymphopenia

(37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).

The most common adverse reactions regardless of causality in Study 1 (n=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%), and in Study 2 (n=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), and lymphopenia (57%).

DRUG INTERACTIONS:• ISTODAX is metabolized by CYP3A4. Avoid

concomitant use with strong CYP3A4 inhibitors and potent CYP3A4 inducers if possible

• Caution should also be exercised with concomitant use of moderate CYP3A4 inhibitors and P-glycoprotein (P-gp, ABCB1) inhibitors

• Physicians should carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin sodium derivatives

USE IN SPECIFIC POPULATIONS:• Because many drugs are excreted in human milk

and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother

• Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution

“Telephone support is justanother way for APNs todo their outreach topatients.”

—Susan Moore, RN,MSN, ANP, AOCN


patient education on adverse effects tochemotherapy and the importance ofreporting serious adverse effects. TheAPN also stressed the importance ofcompleting the chemotherapy regimenas prescribed.“The advanced practice nurse would

do outbound calls to the patients to see how they were doing,” Mooreexplained. “They did not manage the

patient, because that was up to thepractice. Instead, they provided addi-tional information and let the patientknow that there was somebody else outthere that they could come to withtheir questions.”Patients could make as many in bound

calls as they wanted, she added. “Theywere called once per cycle, but theycould call into the call center every day,

twice a day, five times a day if they need-ed some help or support. Some of it waspsychosocial support, but most was aboutthings like ‘I don’t feel well today and Idon’t know what to do.’ The nurseswould listen and give them generaladvice about what they could do to helpthemselves feel better, and then directedthe women back to their physician andthe nurse in the practice office.”

Pharmaceutical records were used toprovide information on adherence in agroup of patients undergoing similar IVchemotherapy without APN telephonesupport, who served as controls.A total of 617 patients consecutively

enrolled in the APN support programfrom January 2006 to March 2010. �

Conference News


Please see Important Safety Information on adjacent page.Please see following pages for Brief Summary of full Prescribing Information.

ISTODAX® is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy

Conference News continued on page 28


ORLANDO—More education aboutassessment and management of car-diotoxicity would strengthen the quality

of nursing care of cancer patients,according to a new study.The study by Wendy Vogel, MSN,

FNP, AOCONP, of Kingsport He ma -tology Oncology Associates, Kings port,Tennessee, and Marilyn Haas, PhD,

ANP-BC, CNS, of CarePartners, Ash e -ville, North Carolina, showed a gap inknowledge among oncology nurses,


Conference News

ISTODAX® (romidepsin) for injectionFor intravenous infusion onlyThe following is a brief summary only; see full prescribing information for complete product information.

1 INDICATIONS AND USAGEISTODAX is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION2.1 Dosing InformationThe recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8 and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the therapy.2.2 Dose ModificationNonhematologic toxicities except alopecia• Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns

to ≤Grade 1 or baseline, then therapy may be restarted at 14 mg/m2. If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2.

• Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2.

• Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction.Hematologic toxicities• Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be

delayed until the specific cytopenia returns to ANC ≥1.5×109/L and/or platelet count ≥75×109/L or baseline, then therapy may be restarted at 14 mg/m2.

• Grade 4 febrile (≥38.5ºC) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to ≤Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2.

2.3 Instructions for Preparation and Intravenous AdministrationISTODAX should be handled in a manner consistent with recommended safe procedures for handling cytotoxic drugs.

4 CONTRAINDICATIONSNone.

5 WARNINGS AND PRECAUTIONS5.1 Monitoring: Laboratory TestsDue to the risk of QT prolongation, potassium and magnesium should be within the normal range before administration of ISTODAX [See Warnings and Precautions (5.3) and Adverse Reactions (6)].5.2 HematologicTreatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lym-phopenia), and anemia; therefore, these hematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary [See Dosage and Administration (2.2) and Adverse Reactions (6)].5.3 Electrocardiographic ChangesSeveral treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [See Adverse Reactions (6)].In patients with congenital long QT syndrome, patients with a history of significant car-diovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.5.4 Use in PregnancyThere are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action, ISTODAX may cause fetal harm when admin-istered to a pregnant woman. A study in rats did not expose pregnant animals to enough romidepsin to fully evaluate adverse outcomes.If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus [See Use in Specific Populations (8.1)].5.5 Use in Women of Childbearing PotentialAdvise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives. An in vitro binding assay determined that romidepsin competes with β-estradiol for binding to estrogen receptors [See Nonclinical Toxicology (13.1)].

6 ADVERSE REACTIONS6.1 Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the

clinical trials of another drug and may not reflect the rates observed in practice.The safety of ISTODAX was evaluated in 185 patients with CTCL in 2 single arm clinical studies in which patents received a starting dose of 14 mg/m2. The mean duration of treat-ment in these studies was 5.6 months (range: <1 to 83.4 months).Common Adverse ReactionsTable 1 summarizes the most frequent adverse reactions (>20%) regardless of causality using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 3.0). Due to methodological differences between the studies, the AE data are presented separately for Study 1 and Study 2. Adverse reactions are ranked by their incidence in Study 1. Laboratory abnormalities commonly reported (>20%) as adverse reactions are included in Table 1.

Table 1. Adverse Reactions Occurring in >20% of Patients in Either CTCL Study (N=185)

Adverse Reactions n (%)Study 1 (n=102) Study 2 (n=83)

All Grade 3 or 4 All Grade 3

or 4

Any adverse reactionNauseaAsthenia/fatigueInfectionsVomitingAnorexiaHypomagnesemiaDiarrheaPyrexiaAnemiaThrombocytopeniaDysgeusiaConstipationNeutropeniaHypotensionPruritusHypokalemiaDermatitis/Exfoliative dermatitisHypocalcemiaLeukopeniaLymphopeniaAlanine aminotransferase increasedAspartate aminotransferase increasedHypoalbuminemiaElectrocardiogram ST-T wave changesHyperglycemiaHyponatremiaHypermagnesemiaHypophosphatemiaHyperuricemia

99 (97)57 (56)54 (53)47 (46)35 (34)23 (23)22 (22)20 (20)20 (20)19 (19)17 (17)15 (15)12 (12)11 (11)7 (7)7 (7)6 (6)4 (4)4 (4)4 (4)4 (4)3 (3)3 (3)3 (3)2 (2)2 (2)1 (<1)

000

36 (35)3 (3)8 (8)

11 (11)1 (<1)1 (<1)1 (<1)1 (<1)4 (4)3 (3)

00

2 (2)4 (4)3 (3)

00

1 (<1)00000

1 (<1)0

2 (2)1 (<1)

000

83 (100)71 (86)64 (77)45 (54)43 (52)45 (54)23 (28)22 (7)19 (23)60 (72)54 (65)33 (40)32 (39)47 (57)19 (23)26 (31)17 (20)22 (27)43 (52)38 (46)47 (57)18 (22)23 (28)40 (48)52 (63)42 (51)17 (20)22 (27)22 (27)27 (33)

68 (82)5 (6)

12 (14)27 (33)8 (10)3 (4)

01 (1)1 (1)

13 (16)12 (14)

01 (1)

22 (27)3 (4)5 (6)2 (2)7 (8)5 (6)

18 (22)31 (37)2 (2)3 (4)3 (4)

01 (1)2 (2)7 (8)8 (10)7 (8)

Serious Adverse ReactionsSerious adverse reactions reported in > 2% of patients in Study 1 were infection, sepsis, and pyrexia. In Study 2, serious adverse reactions in > 2% of patients were infection, su-praventricular arrhythmia, neutropenia, fatigue, edema, central line infection, ventricular arrhythmia, nausea, pyrexia, leukopenia, and thrombocytopenia.Most deaths were due to disease progression. In Study 1, there were two deaths due to cardiopulmonary failure and acute renal failure. In Study 2, there were six deaths due to infection (4), myocardial ischemia, and acute respiratory distress syndrome.DiscontinuationsDiscontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Discontinuations occurring in at least 2% of patients in either study included infection, fatigue, QT prolongation, and dyspnea.

7 DRUG INTERACTIONS7.1 Coumadin or Coumadin DerivativesProlongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Although the interaction potential between ISTODAX and Coumadin or Coumadin derivatives has not been formally studied, physicians should care-fully monitor PT and INR in patients concurrently administered ISTODAX and Coumadin or Coumadin derivatives [See Clinical Pharmacology (12.3)].7.2 Drugs that Inhibit or Induce Cytochrome P450 3A4 EnzymesRomidepsin is metabolized by CYP3A4. Although there are no formal drug interaction stud-ies for ISTODAX, strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromy-cin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, vori-conazole) may increase concentrations of romidepsin. Therefore, co-administration with strong CYP3A4 inhibitors should be avoided if possible. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.

Rx Only

Survey Shows Gaps in Oncology Nurses’ Knowledge aboutCardiotoxicity of Cancer Drugs By Karen Rosenberg


including advanced practice nurses(APNs), treating women with breast can-cer. “This is a wide-open field for oncolo-gy nursing research,” said Vogel, who pre-sented the findings.To evaluate oncology nurses’ knowl-

edge and practice patterns regardingcardiotoxicity in women with early-stage breast cancer treated with humanepidermal growth factor receptor 2

inhibitors/vascular endothelial growthfactor inhibitors, the researchers devel-oped a 24-item survey. Surveys weredistributed before and after the 2009Advanced Practice Nursing Con -ference/Institutes of Learning. Of the248 nurses who responded to the sur-vey, 88% of respondents worked inmedical oncology settings; 26% iden-tified themselves as APNs, 49% as

staff nurses, and 25% as other. Fifty-eight percent worked in the commu-nity outpatient setting, and 56%reported spending at least 1 to 2 hoursper week educating breast cancerpatients about cardiotoxicity. Only 12% of the survey respondents

said they felt very comfortable aboutassessing cardiotoxicity, and 25%reported feeling less than comfortable.

More than 10% of respondents wereuncertain which breast cancer drugscan cause cardiotoxicity, and morethan 20% were unsure whether chemo -therapeutic agents were discontinuedor dose-reduced because of cardiotoxi-city in their practice.Respondents reported that their pri-

mary resource used for managing breastcancer was textbooks (34%) followedby pharmaceutical representatives(18%), national guidelines (18%), andthe Internet (17%). This was concern-ing, Vogel said, because textbooks donot provide the most up-to-date infor-mation, and guidelines prepared by theAmerican Heart Association andAmerican College of Cardiology are notspecific for cancer patients.

Evidence-based guidelines on assess-ment and management of cardiotoxici-ty in patients with cancer are needed,Vogel said. This is becoming increasing-ly important, she explained, because“we’re seeing patients age with cancer.”Better communication is needed be -tween oncologists and cardiologists, sheadded, and “that’s where oncology nurs-es can make a difference—coordinationof care.” �

For more ONS APN/IOL news and pic-tures, see the February 2011 issue of TheOncology Nurse-APN/PA.


Conference News

Co-administration of potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital) may decrease concentrations of romidepsin and should be avoided if possible. Patients should also refrain from taking St. John’s Wort.7.3 Drugs that Inhibit Drug Transport SystemsRomidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If ISTODAX is administered with drugs that inhibit P-gp, increased concentrations of romidepsin are likely, and caution should be exercised.

8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category D [See ‘Warnings and Precautions’ section]. There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action, ISTODAX may cause fetal harm when admin-istered to a pregnant woman. A study in rats did not expose pregnant animals to enough romidepsin to fully evaluate adverse developmental outcomes. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential harm to the fetus.In an animal reproductive study, pregnant rats received daily intravenous romidepsin during the period of organogenesis up to a dose of 0.06 mg/kg/day (0.36 mg/m2/day). This dose in rats is approximately equivalent to 18% the estimated human daily dose based on body surface area and resulted in 5% reduction in fetal weight. Embryofetal toxicities associated with the use of ISTODAX were not adequately assessed in this study.8.3 Nursing MothersIt is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nurs-ing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.8.4 Pediatric UseThe safety and effectiveness of ISTODAX in pediatric patients has not been established.8.5 Geriatric UseOf the 167 patients with CTCL in trials, 23% were >65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out.8.6 Hepatic ImpairmentNo dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharma-cokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)].8.7 Renal ImpairmentNo dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacoki-netics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)].10 OVERDOSAGENo specific information is available on the treatment of overdosage of ISTODAX.Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions.In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable.

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity studies have not been performed with romidepsin. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lym-phoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m2 in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area.Based on non-clinical findings, male and female fertility may be compromised by treat-ment with ISTODAX. In a 26-week toxicology study, romidepsin administration resulted in testicular degeneration in rats at 0.33 mg/kg/dose (2 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were approximately 2% the exposure level in patients receiving the recommended dose of 14 mg/m2/dose. A similar effect was seen in mice after 4 weeks of drug administration at higher doses. Seminal vesicle and prostate organ weights were decreased in a separate study in rats after 4 weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day), approximately 30% the estimated human daily dose based on body surface area. Romidepsin showed high affinity for binding to estrogen receptors in pharmacology studies. In a 26-week toxicology study in rats, atrophy was seen in the ovary, uterus, vagina and mammary gland of females administered doses as low as 0.1 mg/kg/dose (0.6 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were 0.3% of those in patients receiving the recommended dose of 14 mg/m2/dose. Maturation arrest of ovarian follicles and decreased weight of ovaries were observed in a separate study in rats after four weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day). This dose is approximately 30% the estimated human daily dose based on body surface area.

16 HOW SUPPLIED/STORAGE AND HANDLINGKeep out of reach of children.Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [See References (15)].

17 PATIENT COUNSELING INFORMATIONSee FDA-approved patient labeling.17.1 Instructions• Patients should be instructed to report excessive nausea or vomiting, abnormal heart-

beat, chest pain, or shortness of breath to their physician. Patients receiving ISTODAX should seek immediate medical attention if unusual bleeding occurs.

• ISTODAX binds to estrogen receptors. Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives [See Warnings and Precautions (5.5)].

• Patients should be instructed to read the patient insert carefully.

Manufactured for:Celgene Corporation Summit, NJ 07901

Manufactured by:Ben Venue Laboratories, Inc. Bedford, OH 44146

ISTODAX® is a registered trademark of Astellas Pharma, Inc.

U.S. Patents: 4,977,138; 7,608,280; 7,611,724

ISTBVPI.001/PPI.001 03/10

Revised: March 2010

Only 12% of the surveyrespondents said they feltvery comfortable aboutassessing cardiotoxicity,and 25% reported feelingless than comfortable.

Eribulin for Late-stageRefractory Breast CancerThe US Food and Drug Ad min -

istration (FDA) has approvederibulin mesylate (Halaven, Eisai)to treat patients with metastaticbreast cancer who have receivedat least two previous chemothera-py regimens for late-stage disease.Approval was based on a singlestudy of 762 patients who wererandomized to either treatmentwith eribulin or another single-agent therapy chosen by theironcologist.

Recent FDAApproval



CONTINUING EDUCATION

Non–small-cell lung cancer(NSCLC) is the most commontype of lung cancer and is fre-

quently diagnosed at an advanced stage,when effective therapeutic options arelimited. First-line treatment of ad -vanced disease typically includes plat-inum-doublet chemotherapy, which isassociated with a median overall sur-vival (OS) of 8 to 11 months.1Approximately 70% to 80% of

patients receiving first-line chemothera-py will show clinical benefit,2-5 but mostpatients will develop progressive diseasewithin 2 to 3 months of their final cycleof chemotherapy.3,6,7 Unfortunately, clin-ical trials of long-duration platinum-based chemotherapy as first-line treat-ment have consistently shown increasedtoxicity with little or no survivalimprovement.8-13

Second-line treatments are indicatedafter disease progression; however,between one third and one half ofpatients do not receive second-linetherapy.3,6,7,9-11,14-17 Patients may be ineli-gible for second-line therapy because ofrapid disease progression, worseningperformance status, or increased symp-tom burden.7 As a result, a large per-centage of patients do not have the

opportunity to receive effective therapyfollowing first-line treatment. Activemaintenance therapy (ie, treatmentgiven after initial chemotherapy in theabsence of disease progression) should,in theory, improve survival because itallows clinicians not only to provideaccess to more lines of effective treat-ment but also to treat a larger numberof patients, including those who mightotherwise be ineligible for additionallines of therapy.

Trials of maintenance therapySeveral previous phase 3 trials have

shown an improvement in OS withmaintenance therapy with chemothera-peutic agents compared with initiationof second-line therapy at the time ofdisease progression.18Fidias and associates compared im -

mediate with delayed docetaxel afterfrontline therapy with gemcitabine pluscarboplatin in 309 patients with ad -vanced NSCLC.7 They found a statisti-cally significant improvement in pro-gression-free survival (PFS) and anon statistically significant increase inOS with immediate versus delayed doc-etaxel without increased toxicity or de -creased quality of life. Ciuleanu and colleagues compared

maintenance therapy with pemetrexedwith placebo after four cycles of plat-

inum-based chemotherapy in 663patients with advanced NSCLC.6Pemetrexed therapy was well toleratedand improved both PFS and OS.Pemetrexed was the first chemotherapyapproved by the US Food and DrugAdministration as maintenance therapyfor nonsquamous NSCLC (Eli Lillypress release. July 6, 2009).

The SATURN trialErlotinib, an oral epidermal growth

factor receptor (EGFR) tyrosine-kinaseinhibitor, is an established second-linetreatment for advanced NSCLC. Theagent’s proven efficacy coupled with itsoral administration and acceptable tol-erability provide a strong rationale forinvestigation of its potential role asmaintenance therapy.19-24The Sequential Tarceva in Un -

resectable NSCLC (SATURN) trialwas designed to examine the effect oferlotinib as maintenance therapy onPFS in patients with nonprogressive dis-ease following first-line platinum-dou-blet chemotherapy.25 The randomized,

placebo-controlled, phase 3 trial wasconducted at 110 sites in 26 countries.

Study population and protocolThe trial included 889 patients who

had completed four cycles of standardplatinum-doublet chemotherapy with-out disease progression and unaccept-able toxicity. Patients were randomizedto receive erlotinib, 150 mg/day, orplacebo until progression or unaccept-able toxicity or death. Patients werestratified by EGFR immunohistochem-istry status, disease stage, EasternCooperative Oncology Group (ECOG)performance status, chemotherapy regi-men, smoking history, and region.The coprimary end points were PFS

in all analyzable patients regardless ofEGFR status, and PFS in patients withEGFR immunohistochemistry–posi-tive tumors.

ResultsOverall, 437 patients in the erlotinib

group and 447 patients in the placebogroup were evaluable for PFS.

Maintenance Therapy in Patients with Advanced Non–small-cell Lung CancerBy Federico Cappuzzo, MDProfessor and Director, Department of Medical Oncology, Ospedale Riuniti, Livorno, Italy

PROGRAM CE5 • RELEASE DATE: DECEMBER 15, 2010 • EXPIRATION DATE: DECEMBER 15, 2011

ESTIMATED TIME TO COMPLETE: 1.0 HOUR

CONTINUING NURSING EDUCATIONACCREDITATION AND CONTACTHOURS STATEMENTScience Care is approved by the CaliforniaBoard of Registered Nursing, Provider number15559, for 1.0 Contact hour.

METHOD OF PARTICIPATION1. Read the article in its entirety2. Go to www.TheOncologyNurse.com3. Select “Continuing Education”4. Click on this article’s title from the listshown

5. Select “Click here to complete the posttestand obtain a CE certificate online”

6. Complete and submit the CE posttest andCE Activity Evaluation

7. Print your Certificate of Credit

This activity is provided free of charge to participants.

FACULTY DISCLOSURESAs a provider accredited by the California Boardof Registered Nursing, Science Care must ensurebalance, independence, objectivity, and scientificrigor in all its activities. All course directors, fac-ulty, planners, and any other individual in a posi-tion to control the content of this educationalactivity are required to disclose to the audienceany relevant financial relationships with anycommercial interest. Science Care must deter-mine if the faculty’s relationships may influencethe educational content with regard to expositionor conclusion and resolve any conflicts of inter-est prior to the commencement of the educa-tional activity.

Disclosures are as follows:• Frederico Cappuzzo, MD, has nothing todisclose.

• Dawn Lagrosa has nothing to disclose.• Tara L. Rich, MSN, RN, CNP, has nothing todisclose.

• Karen Rosenberg has nothing to disclose.• Jill Stein has nothing to disclose.

The staff of Science Care have nothing todisclose.

DISCLAIMERThe opinions and recommendations expressedby faculty, authors, and other experts whoseinput is included in this program are their ownand do not necessarily represent the viewpointof Science Care or Green Hill HealthcareCommunications, LLC.

COPYRIGHT STATEMENTCopyright © 2010 Science Care. All rightsreserved.

EDITORIAL BOARDFrederico Cappuzzo, MDProfessor and DirectorDepartment of Medical OncologyOspedale Riuniti57124 Leghorn0586 223111Italy

Tara L. Rich, MSN, RN, CNPTaussig Cancer Institute Cleveland Clinic9500 Euclid AvenueCleveland, OH 44195

STATEMENT OF NEEDNon–small-cell lung cancer (NSCLC) is fre-quently diagnosed at an advanced stage. First-line treatment of advanced disease typicallyincludes platinum-doublet chemotherapy;however, after initial clinical benefit mostpatients develop progressive disease within 2to 3 months of their final cycle of chemothera-py. In addition, a large percentage of patientsdo not have the opportunity to receive effectivetherapy following first-line treatment, makingactive maintenance an attractive option.Erlotinib, an oral epidermal growth factorreceptor tyrosine-kinase inhibitor, is an estab-lished second-line treatment for advancedNSCLC. The agent’s proven efficacy coupledwith its oral administration and acceptable tol-erability provide a strong rationale for investi-gation of its potential role as maintenance ther-apy. Although we do not yet know whetherusing an agent like erlotinib as fist-line mainte-nance is better than using the same agent onlyat disease progression, the likelihood of rapidprogression after first-line chemotherapy cou-pled with a lack of means of predicting who willhave the opportunity to receive second-linetherapy strongly supports the use of mainte-nance therapy.

TARGET AUDIENCEAdvanced practice nurses, registered nurses,and other interested healthcare professionals,especially those caring for cancer patients

LEARNING OBJECTIVEAfter completing this activity, the readershould be able to:• Discuss maintenance therapy in patientswith nonprogressive NSCLC following first-line platinum-doublet chemotherapy.

Approximately 70% to80% of patients receivingfirst-line chemotherapy willshow clinical benefit, butmost patients will developprogressive disease within2 to 3 months of their finalcycle of chemotherapy.




COMMENTARY

Using the Results of the SATURN StudyBy Tara L. Rich, MSN, RN, CNPTaussig Cancer Institute Cleveland Clinic, Ohio

Irecently attended a presentation onthe emerging concept of clinicalpathways in the context of health-

care reform. The concept caused meto think about the role of the oncolo-gy practitioner as it parallels that of anartist. It is the concepts of interpreta-tion, patient individuality, and cre-ativity that drive our medical deci-sions when we care for patients. In thepast 2 years, the emerging data on thetreatment of advanced non–small-celllung cancer (NSCLC) have bothincreased our ability to be creative inour decision making and caused con-fusion in doing so.

Standard first-line treatment ofadvanced stage NSCLC is platinum-doublet chemotherapy, which has beenproven by multiple trials, with a medi-an overall survival (OS) of 8 to 11months.1,2 Until recently, the standardof care was to implement second-linetherapy only after disease progression.3,4For many reasons, such as poor per-formance status and rapid progressionof disease for example, some patientsare not able to proceed with second-line therapy. In 2009, maintenancepemetrexed was proved to be superiorto best supportive care after four cyclesof platinum-doublet chemotherapy,with a statistically significant increasein both progression-free survival (PFS)and OS.5 In another study, Fidias andassociates compared immediate versusdelayed second-line docetaxel (75mg/m2, 21-day cycle) after four cyclesof first-line gemcitabine (days 1,8)/carboplatin (day 1) in a phase 3 clin-ical trial, demonstrating a statisticallysignificant difference in PFS, althoughno significant difference in OS, with the

immediate-docetaxel arm.6The Sequential Tarceva in Un -

resectable NSCLC (SATURN) trial, arandomized, placebo-controlled phase 3study, compared maintenance erlotinib(150 mg/day) with placebo, followingfour cycles of platinum-based chemo -therapy.7 PFS was analyzable in 884patients, which is, in my opinion, a sig-nificant sample size considering the tar-get population of advanced NSCLCpatients who were able to receive fourcycles of platinum-doublet chemother-apy without disease progression andmaintain an Eastern Coop erativeOncology Group (ECOG) performancestatus of 0 to 1. The coprimary endpoints were PFS in all patients and PFSin patients with tumors that demon-strated epidermal growth factor receptor(EGFR) protein overexpression byimmunohistochemistry (IHC) status.

The results demonstrated improve-ment in PFS in the erlotinib arm in allanalyzable patients, a median time of12.3 versus 11.1 weeks (hazard ratio[HR], 0.71; P <.0001). The median timeof PFS was exactly the same for thepatients with tumors that were EGFR-positive by IHC (HR, 0.69; P <.0001).Of more interest, the proportion ofpatients with PFS at 6 months was 25%in the erlotinib arm compared with 15%in those receiving placebo. The sub-group analysis of PFS was interesting,demonstrating a benefit with erlotinibcompared with placebo, irrespective ofhistology. Of most importance, OS wassignificantly prolonged with erlotinibversus placebo in the intention-to-treatpopulation (median, 12.0 vs 11.0months; HR, 0.81; P = .0088) in addi-tion to the EGFR-positive-by-IHC pop-

ulation (HR, 0.77; P = .0063), as well asthose without activating EGFR muta-tions (HR, 0.77; P = .0234). We areawaiting the subgroup analysis results ofthe OS data for the EGFR-positive-byIHC population, including those whoreceived second-line erlotinib after dis-ease progression. The SATURN study isthe first to look at tyrosine-kinaseinhibitor targeted therapy in the main-tenance setting after first-line platinum-doublet chemotherapy. Its results haveled to a new indication for erlotinib andopen the door to further studies of tar-geted therapies for maintenance.

Another study, ECOG 4599, intro-duced the use of bevacizumab, a mon-oclonal antibody against the vascularendothelial growth factor, in conjunc-tion with the standard doublet ofpaclitaxel/carboplatin, which wasmaintained until disease progression.Based on the statistically significantresults, it is now standard of care toassess bevacizumab eligibility inpatients beginning first-line platinum-doublet chemotherapy. Typically, cli-nicians continue bevacizumab untildisease progression, because that wasthe study’s design. An as yet unopenedECOG trial, NCT01107626, will in ves-tigate the use of maintenance beva-cizumab versus maintenance peme-trexed. Patients with advanced stageNSCLC will receive four cycles ofpaclitaxel/carboplatin/bevacizumab,followed by randomization to one ofthree maintenance arms: pemetrexedalone, bevacizumab alone, or a peme-trexed/bevacizumab combination.8 Al -though this study is not yet open foraccrual, it should be very interestingto follow its outcomes.

Even with recent trials validatingthe efficacy of immediate second-linedocetaxel, maintenance pemetrexed,and maintenance erlotinib, questionsremain unanswered. Future studies,including NCT01107626, will help usbetter select the appropriate mainte-nance treatment for individual patients.Continued studies in combination withclinical judgment will further assist us indetermining the value of immediate ormaintenance therapy versus treatmentbreaks until disease progression. �

References1. Ramalingam S, Belani CP. Systemic chemotherapyfor advanced non-small cell lung cancer: recentadvances and future directions. Oncologist. 2008;13(suppl 1):5-13.2. Schiller JH, Harrington D, Belani CP, et al; for theEastern Cooperative Oncology Group. Comparison offour chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92-98.3. Sandler A, Gray R, Perry MC, et al. Paclitaxel-car-boplatin alone or with bevacizumab for non-small-celllung cancer. N Engl J Med. 2006;355:2542-2550.4. Socinski MA, Schell MJ, Peterman A, et al. PhaseIII trial comparing a defined duration of therapy versuscontinuous therapy followed by second-line therapy inadvanced stage IIIB/IV non-small-cell lung cancer. JClin Oncol. 2002;20:1335-1343.5. Ciuleanu T, Brodowicz T, Zielinski C, et al.Maintenance pemetrexed plus best supportive care ver-sus placebo plus best supportive care for non-small-celllung cancer: a randomised, double-blind, phase 3 study.Lancet. 2009;374:1432-1440.6. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III studyof immediate compared with delayed docetaxel afterfront-line therapy with gemcitabine plus carboplatin inadvanced non-small-cell lung cancer. J Clin Oncol.2009;27:591-598.7. Cappuzzo F, Ciuleanu T, Stelmakh L, et al; for theSATURN investigators. Erlotinib as maintenancetreatment in advanced non-small-cell lung cancer: amulticentre, randomised, placebo-controlled phase 3study. Lancet Oncol. 2010;11:521-529.8. Bevacizumab or pemetrexed disodium alone or incombination after induction therapy in treating patientswith advanced non-squamous non-small cell lung can-cer. Clinicaltrials.gov identifier NCT01107626. www.clinicaltrials.gov. Accessed August 8, 2010.

After a median follow-up of 11.4months in the erlotinib group and 11.5months in the placebo group, medianPFS was significantly longer with erlo -tinib than with placebo in all evaluablepatients irrespective of EFGR status: 12.3weeks for the erlotinib group versus 11.1weeks for the placebo group (hazard ratio[HR], 0.71; 95% confidence interval[CI], 0.62-0.2; P <.0001). PFS was alsosignificantly prolonged in erlotinib-treated patients with EGFR immunohis-tochemistry–positive tumors (medianPFS, 12.3 vs 11.1 weeks; HR, 0.69; 95%CI, 0.58-0.82; P <.0001). An im prove-ment in PFS was observed in all patientsubgroups regardless of gender, ethnic origin, histology, or smoking status.

Erlotinib was also superior to placebo inPFS for both EGFR mutation–positiveand EGFR wild-type subgroups, with thegreatest benefit shown in patients withEGFR mutation–positive tumors.

OS, a secondary end point, was sig-nificantly prolonged with erlotinib ver-sus placebo in the intention-to-treatpopulation (median 12.0 vs 11.0months; HR, 0.81; 95% CI, 0.70-0.95;P = .0088).

Safety and quality of lifeErlotinib was well tolerated in the

maintenance setting, the incidence andseverity of side effects being slightlylower than those noted in an earlierphase 3 study of second-line and third-

line erlotinib.21 The most commonadverse events were skin rash and diar-rhea, which were usually mild to moder-ate. Skin rash occurred in 37 (9%) of443 erlotinib-treated patients versusnone of 445 placebo-treated patients,and diarrhea occurred in seven (2%)erlotinib patients versus no placebopatients. Serious adverse events weredocumented in 47 (11%) patients ran-

domized to erlotinib versus 34 (8%)patients assigned to placebo. The mostfrequently reported serious event waspneumonia, occurring in seven (2%)patients receiving erlotinib and four(<1%) patients receiving placebo. Mostpatients on erlotinib did not need dosereductions or interruptions.

Quality-of-life measures, which were

Erlotinib was also superior to placebo in PFS for bothEGFR mutation–positive and EGFR wild-typesubgroups, with the greatest benefit shown in patientswith EGFR mutation–positive tumors.



evaluated using the widely validatedFunctional Assessment of CancerTherapy-Lung questionnaire, weresimilar in the erlotinib and placebogroups. Notably, erlotinib-treatedpatients had a longer time to painonset and the need for analgesics.The SATURN study is, to our

knowledge, the first to demonstratethat maintenance therapy with a tar-geted agent after a conventional first-line platinum-based chemotherapyregimen can significantly prolong PFSand OS in ad vanced NSCLC. Basedon the results of the study, the USFood and Drug Administration ap -proved erlotinib for maintenance ther-apy of NSCLC.

Conclusions• A molecularly targeted therapy,given as maintenance immediatelyafter a standard first-line platinum-based chemotherapy regimen, cansignificantly improve the outcomeof metastatic NSCLC.

• Erlotinib significantly improvesPFS in patients who have complet-ed four cycles of standard platinum-doublet chemotherapy without dis-ease progression and unacceptabletoxicity, irrespective of EGFR status.

• Maintenance erlotinib significantlyimproves PFS in patients withEGFR immunohistochemistry–posi-tive tumors.

• The superiority of erlotinib as main-tenance therapy over placebo in

PFS prolongation is not influencedby patient gender, ethnic origin, his-tology, or smoking status.

• Erlotinib is well tolerated whenused as maintenance therapy.

It has not yet been determined, how-ever, whether using an agent as first-line maintenance yields better resultsthan using the same agent at diseaseprogression.

Clinical recommendationsAlthough we do not yet know

whether using an agent like erlotinib asfirst-line maintenance is better thanusing the same agent only at disease pro-gression, the likelihood of rapid progres-sion after first-line chemotherapy cou-pled with a lack of means of predictingwho will have the opportunity to receivesecond-line therapy strongly supports theuse of maintenance therapy. The use oftreatment immediately after first-linechemotherapy increases the number ofpatients who might benefit from activetherapy by postponing disease progres-sion and lengthening survival. �

References1. Ramalingam S, Belani CP. Systemic chemotherapy foradvanced non-small cell lung cancer: recent advancesand future directions. Oncologist. 2008;13(suppl 1):5-13.2. Reck M, von Pawel J, Zatloukal P, et al. Phase III trialof cisplatin plus gemcitabine with either placebo or beva-cizumab as first-line therapy for nonsquamous non-small-lung cancer (AVAiL). J Clin Oncol. 2009;27:1227-1234.3. Brodowicz T, Krzakowski M, Zwitter M, et al; for theCentral European Cooperative Oncology GroupCECOG. Cisplatin and gemcitabine first-line chemo -therapy followed by maintenance gemcitabine or bestsupportive care in advanced non-small cell lung cancer:a phase III trial. Lung Cancer. 2006;52:155-163.

4. Leighl NB, Paz-Ares L, Doullard JY, et al. Randomiedphase III study of matrix metalloproteinase inhibitorBMS-275291 in combination with paclitaxel and car-boplatin in advanced non-small-cell-lung cancer.National Cancer Institute of Canada-Clinical TrialsGroup Study BR.18. J Clin Oncol. 2005;23:2831-2839.5. Williamson SK, Crowley JJ, Lara PN Jr, et al. PhaseIII trial of paclitaxel plus carboplatin with or withouttirapazamine in advanced non-small-cell lung cancer:Southwest Oncology Group Trial S0003. J Clin Oncol.2005;23:9097-9104.6. Ciuleanu T, Brodowicz T, Zielinski C, et al.Maintenance pemetrexed plus best supportive care ver-sus placebo plus best supportive care for non-small-celllung cancer: a randomised, double-blind, phase 3 study.Lancet. 2009;374:1432-1440.7. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III studyof immediate compared with delayed docetaxel afterfront-line therapy with gemcitabine plus carboplatin inadvanced non-small-cell lung cancer. J Clin Oncol.2009;27:591-598.8. Socinski MA, Schell MJ, Peterman A, et al. Phase IIItrial comparing a defined duration of therapy versuscontinuous therapy followed by second-line therapy inadvanced stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002;20:1335-1343.9. von Plessen C, Bergman B, Andresen O, et al.Palliative chemotherapy beyond three courses conveysno survival or consistent quality-of-life benefits inadvanced non-small-cell lung cancer. Br J Cancer.2006;95:966-973.10. Barata FJ, Parente B, Teixeira E, et al. Optimal dura-tion of chemotherapy in non-small-cell lung cancer:multicenter, randomized, prospective clinical trial com-paring 4 vs 6 cycles of carboplatin and gemcitabine[abstract]. J Thoracic Oncol. 2007;2(suppl 4):S666.11. Park JO, Kim SW, Ahn JS, et al. Phase III trial oftwo versus four additional cycles in patients who arenonprogressive after two cycles of platinum-basedchemotherapy in non-small-cell lung cancer. J ClinOncol. 2007;25:5233-5239.12. Smith IE, O’Brien MER, Talbot DC, et al. Durationof chemotherapy in advanced non-small-cell lung can-cer: a randomized trial of three versus six courses of mit-omycin, vinblastine, and cisplatin. J Clin Oncol. 2001;19:1336-1343.13. Pfister DG, Johnson DH, Azzoli CG, et al; for theAmerican Society of Clinical Oncology. AmericanSociety of Clinical Oncology treatment of unresectablenon-small-cell lung cancer guideline: update 2003. J Clin Oncol. 2004;22:330-353.14. Belani CP, Barstis J, Perry MC, et al. Multicenter,randomized trial for stage IIIB or IV non-small-cell lungcancer using weekly paclitaxel and carboplatin followedby maintenance weekly paclitaxel or observation. J ClinOncol. 2003;21:2933-2939.

15. Pirker R, Pereira JR, Szczesna A, et al; for the FLEXStudy Team. Cetuximab plus chemotherapy in patientswith advanced non-small-cell lung cancer (FLEX): anopen-label randomised phase III trial. Lancet. 2009;373:1525-1531.16. Scagliotti GV, Parikh P, von Pawel J, et al. Phase IIIstudy comparing cisplatin plus gemcitabine with cis-platin plus pemetrexed in chemotherapy-naïve patientswith advanced-stage non-small-cell-lung cancers. J ClinOncol. 2008;26:3543-3551.17. Stinchcombe TE, Socinski MA. Treatment para-digms for advanced stage non-small-cell lung cancer inthe era of multiple lines of therapy. J Thoracic Oncol.2009;4:243-250.18. Stinchcombe TE, Evans T. Role of maintenancetherapy in advanced non-small-cell lung cancer. In:American Society of Clinical Oncology. 2010Educational Book. Alexandria, VA: American Society ofClinical Oncology; 2010:297-302.19. Azzoli CG, Baker S Jr, Temin S, et al; for theAmerican Society of Clinical Oncology. AmericanSociety of Clinical Oncology Clinical PracticeGuideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2009;27:6251-6266.20. D’Addario G, Felip E; for the ESMO GuidelinesWorking Group. Non-small-cell lung cancer: ESMOclinical recommendations for diagnosis, treatment andfollow-up. Ann Oncol. 2009;20(suppl 4):68-70.21. Shepherd FA, Pereira JR, Ciuleanu T, et al; for theNational Cancer Institute of Canada Clinical TrialsGroup. Erlotinib in previously treated non-small-celllung cancer. N Engl J Med. 2005;353:123-132.22. Bezjak A, Tu D, Seymour L, et al. Symptomimprovement in lung cancer patients treated witherlotinib: quality of life analysis of the National CancerInstitute of Canada Clinical Trials Group Study BR.21.J Clin Oncol. 2006;24:3831-3837.23. Ramalingam S, Sandler AB. Salvage therapy foradvanced non-small cell lung cancer: factors influenc-ing treatment selection. Oncologist. 2006;11:655-665.24. Gatzemeier U, Pluzanska A, Szczesna A, et al. PhaseIII study of erlotinib in combination with cisplatin andgemcitabine in advanced non-small-cell lung cancer:the Tarceva Lung Cancer Investigation Trial. J ClinOncol. 2007;25:1545-1552.25. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinibas maintenance treatment in advanced non-small-celllung cancer: a multicentre, randomized, placebo-con-trolled phase 3 study. Lancet Oncol. 2010;11:521-529.

Jill Stein contributed to the preparation ofthis article.


CONTINUING EDUCATION

Continued from page 31

Maintenance Therapy in Patients with Advanced Non–small-cell Lung Cancer

LUNG CANCER

Low-dose CT Screening Found to Reduce Lung Cancer Deaths in Large StudyBy Karen Rosenberg

Alarge National Cancer Institute(NCI)-sponsored study hasshown for the first time that a

screening method can reduce deathsfrom lung cancer by detecting cancersat relatively early stages.The National Lung Screening Trial

(NLST), a randomized national trialinvolving more than 53,000 currentand former heavy smokers aged 55 to74 years, compared the effects of twoscreening methods for lung cancer—low-dose helical computed tomogra-phy (CT) and standard chest radiogra-phy—on lung cancer mortality. Resultsshowed a highly significant 20% reduc-tion in lung cancer deaths among trialparticipants screened with low-dosehelical CT.“A validated approach that can re -

duce lung cancer mortality by even20% has the potential to spare very sig-nificant numbers of people from the rav-ages of this disease,” said NCI DirectorHarold Varmus, MD.NLST participants were required to

have a smoking history of at least 30pack-years and were either current orformer smokers without signs, symp-toms, or history of lung cancer atenrollment. Participants were random-ly assigned to receive three annualscreens with either low-dose helicalCT (often referred to as spiral CT) orstandard chest radiography. Screeningwas done at enrollment and at the endof their first and second years on thetrial, and participants were then fol-lowed for up to another 5 years. As of October 20, 2010, 354 partici-

pants in the CT arm of the study haddied of lung cancer compared with 442of those in the chest radiography group.The Data and Safety Monitoring Boardconcluded that this 20.3% reduction inlung cancer mortality met the standardfor statistical significance.“The fact that low-dose helical CT

provides a decided benefit is a result thatwill have implications for the screeningand management of lung cancer formany years to come,” said ChristineBerg, MD, NLST, project officer for theLung Screening Study at NCI.An ancillary finding was that all-cause

mortality was 7% lower in participantsscreened with low-dose helical CT thanin those screened with chest radiography.Further analysis will be required to fullyelucidate the reason for this difference.

The investigators do not recommendhelical CT screening for all smokers,pointing out that it has several possibledisadvantages, including the cumula-tive effects of radiation from multipleCT scans; false-positive results leadingto further tests and procedures withpossible complications; and costs andanxiety related to the screeningprocess itself. They note too that thepopulation enrolled in this study was ahighly motivated and primarily urbangroup that was screened at major med-ical centers, and the results may notaccurately predict the effects of recom-mending low-dose helical CT scanningfor other populations.Further information about the NLST

can be found at www.cancer.gov/newscenter/qa/2002/nlstqaQA. �


TON_December 2010_FINAL_TON 12/6/10 2:22 PM Page 32

VELCADE and Millennium are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139

Copyright © 2010, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA V-10-0196 11/10


TARGET AUDIENCEThis activity is intended for hematologists, oncologists and others whoare involved with the care of patients with Chronic LymphocyticLeukemia (CLL).

STATEMENT OF NEEDCLL is the most common type of leukemia in the United States, withover 15,000 new cases per year, characterized by the accumulation ofmonoclonal B cells in the bone marrow, peripheral blood, and lymphoidtissue. Primarily a disease of the elderly, the median survival for CLLvaries substantially: many patients survive more than 10 years after diagnosis, but a subset of symptomatic patients have shorter lifeexpectancies—in the range of 1.5 to 6 years. The clinical/research bodyof knowledge in CLL is rapidly changing and represents a challenge forthe whole treatment team.

EDUCATIONAL OBJECTIVESOn completion of this activity, participants should be able to:

• List the essential steps in diagnosis and treatment planning of theCLL patient

• Select CLL treatment regimens based on patient characteristics• Define data supporting the benefit/risk ratio of upfront, relapsed,

and refractory CLL setting• Define strategies to manage fludarabine-resistant CLL• Describe emerging therapies in CLL

www.coexm.com/ace02.aspLOG ON TODAY TO PARTICIPATE

Release Date: April 29, 2010Expiration Date: April 28, 2011

In collaboration with

FACULTYNeil E. Kay, MD Professor Department of Medicine Mayo ClinicRochester, Minnesota

Michael Keating, MDCourse ChairProfessor of Medicine �Deputy Department Chairman�Department of Leukemia�M.D. Anderson Cancer Center�Houston, Texas

This activity has been approved for 1.5 AMA PRA Category 1 Credits™. For further information and to participate, please go to: www.coexm.com/ace02.asp

This activity is supported by an educational grant fromGenentech BioOncology and Biogen Idec.

Chronic Lymphocytic LeukemiaThe Essentials of Patient Care

A TON_December 2010_FINAL_TON 12/6/10 11:21 AM Page 34




DECEMBER 2010 www.AONNonline.org VOL 1, NO 7

Lillie Shockney, RN, BS, MASJohns Hopkins Breast CenterJohns Hopkins UniversitySchool of MedicineBaltimore, Maryland

Sharon Gentry, RN, MSN, AOCN,CBCNDerrick L. Davis ForsythRegional Cancer CenterWinston-Salem, North Carolina

Nicole Messier, RNVermont Cancer CenterBurlington, Vermont

Pamela Matten, RN, BSN, OCNSt. Joseph HospitalOrange, California

Elaine Sein, RN, BSN, OCN, CBCNFox Chase Cancer Center PartnersRockledge, Pennsylvania

Tricia Strusowski, MS, RNHelen F. Graham Cancer CenterChristiana Care Health SystemNewark, Delaware

Linda Fleisher, MPH, PhD(c)Fox Chase Cancer CenterCheltenham, Pennsylvania


Jay R. Swanson, RN, BSN, OCNSaint Elizabeth Cancer InstituteLincoln, Nebraska

Carol Lewis, RN, BSN, OCN, CRNIMemorial HermannThe Woodlands, Texas


Leadership Council


AONN Staff

www.AONNonline.org

GUIDE OUR PATHStart a Chapter/Affiliate

Join a Committee

The George Washington CancerInstitute (GWCI) recently re -ceived a $2.4-million grant from

the DC Cancer Consortium to estab-lish and coordinate a City-wide PatientNavi gation Network (CPNN) inWash ington, DC. The CPNN will create a seamless,

cohesive framework for coordination ofcancer care throughout the city to ensurethat all city residents get appropriate can-cer screening and treatment regardless oftheir ability to pay. The network will alsohelp patients identify support servicesthroughout the cancer continuum, in -cluding posttreatment survivorship. Twenty-five separate institutions,

including hospitals, cancer centers, andcommunity organizations in theWashington, DC, area are members of





Continued on page 2

CARE COORDINATION

City-wide Patient Navigation NetworkCoordinates Washington, DC, Cancer CareBy Karen Rosenberg

The Center for the Advancementof Cancer Survivorship, Navi -gation, and Policy (caSNP), a

collaboration of the George Wash ingtonCancer Institute (GWCI) and the uni-versity’s School of Public Health andHealth Services Department of HealthPolicy, was established in 2009 with support from Pfizer and the PfizerFoundation. The center’s goals are toadvance patient navigation and cancersurvivorship efforts both locally andnationally through training, research,

policy analysis, and education. caSNP grew out of the understanding

that there is “overlap between patientnavigation, survivorship, and policy andboth of these intersect with local andnational healthcare policy,” explainedSteven Patierno, PhD, executive directorof the GWCI. “We wanted to create aplatform to talk about navigation and sur-vivorship in the context of policy in aunited program.” The center offers training programs at

three levels:

• Navigation training is designed fornavigators, including nurses, socialworkers, and lay persons. Traineesfrom institutions across the coun-try learn about barriers that affecttheir patients, are trained tolaunch or improve programs, andgain tools for implementing insti-tutional change.

• Executive-level training is de -signed for chief executive officers,chief financial officers, hospital

NAVIGATION TRAINING

Center Provides Platform for Discussion ofCancer Survivorship, Navigation, and Policy By Karen Rosenberg

Continued on page 2

“The CPNN will create a seamless,cohesive framework for coordination ofcancer care throughout the city.”

—Steven Patierno, PhD

TON_December 2010_FINAL_TON 12/6/10 11:21 AM Page B1

www.AONNonline.org2 December 2010 I VOL 1, NO 7

not provide clinical services, the navi-gator at the advocacy group can put thepatient’s information into the secure logand navigate that patient to a screeningsite, let’s say a mammography center.The navigator at the mammographycenter has access to that same patientcode, opens up the log and continues

entering what he or she did to navigatethe patient. If the patient has a suspi-cious finding and needs a biopsy at a comprehensive medical center, thescreening navigator connects thepatient to a navigator embedded inone of the medical centers, who alsohas access to the patient’s de-identifieddata and can continue the process. Wecontinue that all the way through untilthe survivorship period. It’s an absolute-ly remarkable program; it’s unprece-dented anywhere else.”

Patient Navigation ResearchProgramThe CPNN is an outgrowth of the

Patient Navigation Research Program(PNRP), a 5-year national study on theeffectiveness of patient navigationfunded by the National CancerInstitute and the American CancerSociety. GWCI is one of nine sitesthroughout the country participating inthe program. Data are being collected toanswer two key questions: (1) Doespatient navigation narrow the windowbetween a suspicious finding and diag-nostic resolution? And (2) Does it nar-row the window between diagnosis andthe onset of treatment?

The DC PNRP was launched in 2005and two major concepts have emerged,said Patierno. “The first is what we calllongitudinal navigation because webegan to understand that the barriersthat affect access to care during treat-ment also extend to screening and post-treatment into survivorship. So westarted talking about longitudinal navi-gation,” he explained. “We startedpropagating a model whereby patientnavigation could be extended into theoutreach arm of the continuum ofhealthcare. Not that the navigatorswould become outreach specialists butthey would be coupled with outreachworkers to help people overcome barri-ers to accessing screening. Then westarted using navigators during the tran-sition from active care into the post-treatment survivorship period, whomwe call survivorship navigators.”The other unique aspect of the pro-

gram, is network navigation, whichPatierno says “is completely unique toWashington, DC” although other citiesare looking into it. “We were able tounite through PNRP, five otherwiseunaffiliated, competing medical centers,and four community advocacy organiza-tions to all work together in this partic-

ular area. We created a seamless net-work where patients could actually benavigated within and between other-wise unaffiliated medical centers inWashington, DC.” Patierno has worked closely with

Harold Freeman, who developed theconcept of navigation to help patients inunderserved communities overcome bar-riers to healthcare and reduce disparitiesin the care received. “Regardless ofwhere patients are in the care continu-um, there are barriers and the role of thenavigator is to overcome those barriers,”he notes. “That’s the critical issue. Thatmeans that patient navigation should beavailable to all patients regardless of theirrace or socioeconomic status, but it alsomeans that the patients who will benefitthe most from patient navigation will bethe underserved and those who do nothave the resources that others do.” The concept of patient navigation is

“very powerful,” he says. “You wouldhave to look very long and very hard tofind a new concept in healthcare thatintegrated itself into the healthcare con-sciousness faster than patient navigation.It has not just rolled across the country;it has steamrolled across the country. Wejust need to steer it a little bit.” �

City-wide Patient Navigation Network... Continued from cover

Center Provides Platform forDiscussion... Continued from cover

administrators and other mid-levelsupervisors. “We give them businessmodels, we give them tools for fol-low-up, everything they need tolaunch a program, maintain a pro-gram, and build a sustainable pro-gram,” Patierno said.

• The policy scholars program forphysicians, nurses, and research sci-entists addresses health policy and itsimpact on cancer care, throughoutthe continuum of cancer care.

In addition to these training programs,

caSNP engages in health policy analysis.Patierno and his caSNP colleagues havecontributed a chapter on survivorshipand healthcare with, which will beincluded in a book to be published inJanuary (Feverstein M, Ganz P, eds.Quality Health Care for Caner Survivors.Sprirger). And the GWCI in collabora-tion with the American Cancer Societyhas received a grant from the Centersfrom Disease Control and Prevention tolaunch a virtual national cancer sur-vivorship resource center. �

Chelsea Phelps, American Cancer Society/George Washington Cancer Institute navigatorspeaks with a patient in the waiting area of theGeorge Washington University/Medical FacultyAssociates Katzen Cancer Center.

caSNP staff at the First Annual Survivorship Symposium. Left to right: Melekte Truneh, MBA; Mandi Pratt Chapman, MA; Becky Beauregard; and Amina Gilyard, MEd.

BREAST CANCER

Patient NavigationImproves MammographyRates in the Inner CityBy Dawn Lagrosa

Patient navigation in the primarycare setting can improve adher-ence to biennial mammograms

among inner-city, low-income, minori-ty populations, based on the results ofa study by researchers at BostonUniversity School of Medicine. Thestudy also demonstrates the feasibilityof adopting patient navigation to sim-ilar urban safety-net settings acrossthe country.At the primary care level, 3895

women aged 51 to 70 years who werepatients of record at internal medicinepractices located at an academic safe-ty-net hospital were randomized toeither navigation intervention or usualcare (controls). For the interventiongroup, patients who underwent theirlast mammogram more than 18months previously received telephonecalls and reminder letters. Participants consisted of 71% racial/

ethnic minorities and 23% non-English speakers; 63% had public or no health insurance. Mammographyadherence rates rose in the interven-

tion group, from 78% at baseline to87% after intervention. For the con-trol group, rates remained somewhatstable, dropping slightly from 78% atbaseline to 76% after the interventionperiod. Hispanic women showed highrates of mammography compliance inboth the intervention (85%) and con-trol (83%) groups.This study was published online

October 8 in the Journal of GeneralInternal Medicine. �

©iS

tockp

ho

to.c

om

/art

-4-a

rt

TON_December 2010_FINAL_TON 12/6/10 12:05 PM Page B2

December 2010 I VOL 1, NO 7 3www.AONNonline.org

A2007 report by the Institute ofMedicine (IOM) concludedthat psychosocial issues creat-

ed or exacerbated by cancer are “palpa-ble, important, and potentially crip-pling” but can be effectively addressedby services and interventions. Thereport, Cancer Care for the WholePatient: Meeting Psychosocial HealthNeeds, also acknowledged that appro-priate psychosocial care is the “excep-tion rather than the rule in cancer caretoday,” and a study by the OncologyNursing Society (ONS) bore this out.The ONS research, presented at the

annual meeting of the American Psycho - social Oncology Society, found thatalmost two thirds of oncology nurseswere unfamiliar with the IOM reportand its recommendations (Table 1),according to Tracy Gosselin, RN,MSN, AOCN, director of oncologyservices at Duke University Hospital,Durham, North Carolina.“Although nurses may assess patients’

needs, multiple barriers pertaining toindividuals and institutions still existrelated to communication, knowledgeof IOM recommendations, and re -sources,” Gosselin said. “These barriersmay impair their ability to provide thenecessary psychosocial care to patientsand their families.”The web-based survey was developed

by the ONS Psychosocial Project andthe ONS Research Team. Questionswere aligned with recommendationsfrom the IOM report. The 34-item sur-vey was pilot-tested on 76 ONS mem-bers, more than half of whom had amaster’s degree in nursing and wereadvanced practice nurses.The pool of candidates has since

been expanded to 400 nurses, but thepresentation was based on the 76 inthe pilot study.

Seventy-one percent were aged 45 to59 years, 97% worked with adults, 56%worked in the outpatient setting, 31%worked in the inpatient setting, and 74%worked in frontline patient care.Regarding their knowledge of the

IOM report, 64% were “not at all” or“not very” familiar with the report,whereas only 34% were “somewhat” or“very” familiar with it, she reported.It is important to note that only

12% reported that someone in theirwork setting had communicated ortaken action based on the IOM recom-mendations. Forty-two percent had nottaken action, and 41% were unsure ifany action had been taken.The responsibility for the provision of

psychosocial health services typically fellto a social worker (43%), followed by anurse (17%), an ad vanced practice nurse(17%), a be havioral health professional(9%), a physician (3%), a pastor or spir-itual care counselor (3%), or anotherindividual (7%).The nurses used a variety of methods

for assessing and identifying the psy-chosocial issues and needs of theirpatients, but discussion with thepatient was by far the most common(Table 2). Thirty-six percent said theyapplied evidence-based resources forpsychosocial care to their practices.

“They used a variety of assessments,but the best evidence for this is from theNCCN [National ComprehensiveCancer Network], which developed theDistress Thermometer. This incorpo-rates symptomatology, spirituality, eco-nomics, transportation, and other ele-ments of stress and coping. Only 13%were using this,” Gosselin pointed out.Perhaps some of the insufficiency in

psychosocial service can be attributedto the multiple barriers faced byhealthcare providers, including lack oftime at work (49%), lack of patientand family access to providers (41%),lack of insurance coverage or high costof services (41%), and lack of commu-nity re sources (29%), she added.“The key barriers were related to

having time to assess and provide theseservices, to lack of insurance coverage,and to access to suitable providers,” shenoted. “We know that the bulk of can-cer patients are not treated in academ-ic medical centers like ours. If you area rural healthcare provider, do youhave someone to refer these patientsto? This is another important issue.”Only 20% cited a lack of experience

in assessment or screening tools for dis-tress as a barrier to the delivery of psy-chosocial care.These results were incorporated into

a 3-year plan that has been submittedto the ONS, which includes recom-mendations for advocacy, education,and research related to the integrationof evidence-based practices into psy-chosocial care delivery. �

PSYCHOSOCIAL ISSUES

Most Oncology Nurses Unfamiliar with IOM Reporton Caring for the Whole PatientBy Caroline Helwick

Table 2 Tools and Methods Used to Assess Psychosocial Needs (n = 76)

Method N (%)Interview and discussion 59 (78)Numeric, Likert, or visual analog scale 20 (26)Activities of daily living scale 15 (20)No specific instrument 15 (20)National Comprehensive Cancer Network Distress Thermometer

10 (13)

Depression scale 9 (12)Anxiety scale 3 (4)Social support scale 3 (4)Acculturation scale 2 (3)Caregiver strain index 2 (3)Other 6 (8)

Institute of Medicine’sStandard of Care for MeetingPsychosocial Health Needs

All cancer care should ensure theprovision of appropriate psychosocialhealth services by:• Facilitating effective communicationbetween patients and care providers

• Identifying each patient’s psycho -social health needs

• Designing and implementing a planthat links the patient with needed psychosocial services, coordinatesbio medical and psychosocial care,and engages and supports patients inmanaging their illness and health

• Systematically following up on,reevaluating, and adjusting plans

Table 1

Academy of Oncology Nurse Navigators (AONN) is pleased to announce the extension of its official publication into 2011.

If you have ever wanted to be a published author or have simply been looking for the right journal to publish your work,

regarding these two specific topic areas, the wait is over.

Please submit manuscripts online at www.AONNonline.org/manuscripts

Want to get more involved?Submit your CV/Bio to be considered for expert advisory

board positions to [email protected].

If you have any questions about AONN or the Journal of Oncology Navigation & Survivorship, please contact

Sean T. Walsh, Executive Director of AONN, at

[email protected].

Submit a Manuscript Today!




The ONLY journal focused on patient navigation and survivorship care in oncology patients.

Almost two thirds ofoncology nurses wereunfamiliar with the IOMreport and itsrecommendations.


A2007 report by the Institute ofMedicine emphasized that psy-chosocial support is an integral

part of caring for cancer patients but isthe exception, not the rule, in mostcancer centers. Not so at the ClevelandClinic’s Taussig Cancer Institute, whichanswered this need by embedding aninterdisciplinary psychosocial oncologyprogram into its cancer care system.Isabel Schuermeyer, MD, psychiatrist

and director of the program, describedthe rationale for the psychooncologyprogram and how it has improved can-cer care at the Taussig Cancer Institute,which sees approximately 1400 newpatients a year and 250 per day.“Historically, the way things worked

at our institution, and probably at mostinstitutions, was for our psychosocialoncology services to function as inde-pendent practitioners in their own silos,with little collaboration with eachother,” she said. “Psychiatry referrals forcancer patients were made directly tothe Department of Psychiatry, with await time up to 3 months.”

Developing the program“What we have done is to develop a

collaborative way of bringing a number of

services together,” she said. These servic-es include not only counseling but alsodisparities outreach, spiritual care, sup-port groups, and other auxiliary services.The first step was to expand the exist-

ing services to include the provision offirst-line mental health services and psy-chotherapy. The program now employsone psychiatrist (Schuermeyer), eightsocial workers, and a support staff thatincludes nutrition counseling, spiritualcare, disparities outreach, and a “4thAngel Mentoring Program.”This cut the wait time for a mental

health referral to 1 week, although thishas recently crept back up to 1 month,she acknowledged. Schuermeyer per-sonally has more than 700 patient-visitsa year for a variety of conditions, most-ly related to the cancer diagnosis.There is now a clear protocol for

psychiatry referrals and a more formalstructure for psychotherapy and fortriage. There is also a user-friendly refer-ral pro cess for medical staff, and patientscan self-refer themselves as well, througha call center.Social workers offer supportive coun-

seling and assistance with communityresources. They also perform the clini-cal assessments of patients, referring non-

emergency cases for oncology social workintervention and emergency cases to thepsychiatrist for prompt intervention.The psychosocial services are noted inthe patients’ electronic medical record sothat oncologists remain informed. Effortsare made to maintain confidentiality indialogue, she added.Psychotherapy is provided free of

charge to patients who are in cancertreatment if their psychiatric diagnosisis believed to be secondary to theircancer diagnosis (ie, difficulty coping,etc), she said. One person is in chargeof maintaining the schedule of referralsand ensuring that the proper protocolis followed.

Administration was onboard fromthe start“The administration was supportive

from the beginning,” Schuermeyer said.

“Dr. Derek Raghavan, the institute’schair, is dedicated to the psychoso-cial oncology concept.”The first steps were to develop

strong interdepartmental collabora-tion, reallocate social workers withinthe cancer center, and add a psychia-trist, with the goal of building a stronginterdisciplinary service. Next, theelectronic medical record was modi-fied to include a schedule for psy-chooncology services, and standardoperating procedures were developed.Protocols for handling emergencieswere also developed. The programstays on track through monthly staffmeetings.“The result of this is that our pro -

viders now work together to bettermanage patients and to optimize theirpsychosocial care, all within one can-cer center,” she said. �

www.AONNonline.org4 december 2010 I VOL 1, NO 7

PSYCHOSOCIAL ISSUES

Integrative Psychooncology Services: How theCleveland Clinic Did ItBy Caroline Helwick

SAN DIEGO—One third of breastcancer survivors who received breast-conserving treatments (lumpectomy andradiation) rate the appearance of theirposttreatment breast as “fair” or “poor” incomparison with their untreated breast,according to a study presented at the52nd annual meeting of the AmericanSociety for Radiation Oncology. In addition, one fifth of patients re -

ported complications, including chron-ic pain in their breast or arm, and loss ofarm or shoulder flexibility followingtreatment.The study is the first to examine

patients’ impressions of the cosmeticappearance of their breast followingtreatment. These findings differ dramat-ically from those of previous studies, inwhich clinicians were more likely tolabel posttreatment breasts as “good” or“excellent” in appearance. The authorsof this study say that these findings shedlight on how patients’ treatment expec-tations may differ from their physicians’

and reveal a need for additional patienteducation about potential outcomes.“Most patients are ultimately happy

they were able to preserve their breast,but our study shows that often how theyfeel about the way they look after treat-ment is not as good as doctors would

have predicted,” said lead study authorChristine Hill-Kayser, MD, assistantprofessor of radiation oncology at theUniversity of Pennsylvania School ofMedicine, Philadelphia.Among the 503 patients surveyed

who had a lumpectomy followed by

radiotherapy, 16% rated cosmesis as“excellent”; 52%, “good”; 30%, “fair”;and 2%, “poor.” Interestingly, 43% ofwomen reported chronic skin or soft-tis-sue changes, 22% chronic pain in thebreast or arm, 21% a loss of arm orshoulder flexibility, and 8% chronicswelling. The study data were collected from

patients who voluntarily created anonline survivorship care plan using theLIVESTRONG Care Plan, which pro-vides users with an easy-to-follow roadmap for managing their health as theyfinish treatment and transition to life asa cancer survivor.“It’s very important that cancer sur-

vivors be empowered by information.They should be aware not only of thepossible complications associated withtheir treatment, but also that there arethings that they can do about many ofthem,” said Hill-Kayser.Currently, more than 50% of women

with stage I or II breast cancer undergo

both lumpectomy and radiation. Thesepatients commonly report scarring, skinpuckering, changes in color or textureof skin, size or shape asymmetry be -tween the treated and untreated breast,and nipple distortion. Although it maynot be possible to correct all of theseproblems, Hill-Kayser says a variety oftherapies are available for women withtreatment complications, includingphysical therapy and weight trainingregimens for patients who experiencethe painful arm-swelling conditioncalled lymphedema and shoulder painand/or stiffening.The findings from this study may be

of particular interest to oncology nurses.“As cure rates for breast and other can-cers continue to improve, attention tosurvivorship issues is more importantthan ever before,” said Hill-Kayser.“Understanding more about the waythat survivors feel after their treatmentis one step toward helping patients liveas well as possible after cancer.” �

SURVIVORSHIP

Survivors Often Dissatisfied with Breast-conservingTreatment ResultsBy John Schieszer

The first steps were to develop stronginterdepartmental collaboration, reallocate socialworkers within the cancer center, and add apsychiatrist, with the goal of building a stronginterdisciplinary service.

As cure rates for breastand other cancerscontinue to improve,attention to survivorshipissues is more importantthan ever before.


Current activities at www.COEXM.com include:

� ��

��

��

��

��

��

��

��

�� CONTINUING EDUCATION CREDITS

��

��



Medications Used for the Treatment of Hematologic Cancers

Current MedicareFDA- code price allowableapproved Compendia listed (AWP-based (ASP + 6%), CPT ®

generic (Brand) HCPCS code: for multiple off-label use for pricing), effective effective administrationname code description myeloma multiple myelomaa 11/1/10 10/1/10-12/31/10 codesarsenic trioxide J9017: injection, � $47.51 $37.25 96413, 96415(Trisenox) arsenic trioxide, 1 mgbetamethasone J8499b: prescription drug, � NDC NDC N/A(Celestone) oral, non-chemotherapeutic, level level

not otherwise specified pricing pricingbetamethasone J0702: injection, � $8.00 $6.24 11900, 11901, 20600,acetate and betamethasone acetate 20605, 20610, 96372betamethasone 3 mg, and sodium phosphate betamethasone sodium (Celestone Soluspan) phosphate 3 mgbortezomib J9041: injection, � $46.66 $39.29 96409(Velcade) bortezomib, 0.1 mgcarmustine J9050: injection, � $205.69 $175.88 96413, 96415(BiCNU) carmustine, 100 mgcisplatin J9060: cisplatin, powder � $4.33 $1.50 96409, 96413, 96415(Platinol AQ) or solution, per 10 mgcisplatin J9062: cisplatin, � $21.66 $7.49 96409, 96413, 96415(Platinol AQ) 50 mgcortisone acetate J8499b: prescription drug, � NDC NDC N/A(Cortone) oral, non-chemotherapeutic, level level

not otherwise specified pricing pricingcyclophosphamide J8530: cyclophosphamide, � $2.09 $0.83 N/A(Cytoxan) oral, 25 mgcyclophosphamide J9070: cyclophosphamide, � $10.57 $5.96 96409, 96413, 96415(Cytoxan) 100 mg (all 100-mg NDCs

inactive; 500-mg NDCs used to calculate code price)

O N C O L O G Y D R U G C O D E SSupplied by: RJ Health Systems

The following sections will assist healthcare pro-fessionals and payers by providing appropriate cod-ing, billing, and reimbursement information asso-ciated with the management of multiple myelomaor myelodysplastic syndromes.

The following sections include:• Associated ICD-9-CM codes used for the

classification of multiple myeloma ormyelodysplastic syndromes

• Drugs that have been FDA-approved in thetreatment of multiple myeloma or myelo -dysplastic syndromes

• Drugs that are Compendia listed for off-labeluse for breast cancer based on clinical stud-ies that suggest beneficial use in some cases.Please note: if a check mark appears in theFDA column it will NOT appear in thecompendia off-label use column

• Corresponding HCPCS/CPT® codes and code descriptions

• Current Code Price (AWP-based pricing)• Most recent ASP plus 6% (Medicare allow-

able), if applicable • Possible CPT® Administration Codes for

each medication

Associated ICD-9-CM Codes Used for Multiple Myeloma203 Multiple myeloma and immunoproliferative neoplasms

The following fifth-digit subclassification is for use with category 203:0 without mention of having achieved remission

>Failed remission<1 in remission2 in relapse

203.0 Multiple myelomaKahler’s diseaseMyelomatosisexcludes: solitary myeloma (238.6)

203.1 Plasma cell leukemiaPlasmacytic leukemia

203.8 Other immunoproliferative neoplasms

Multiple MyelomaMultiple myeloma is a type of cancer that begins in plasma cells (white blood cells that produce antibodies).






generic (Brand) HCPCS code: for multiple off-label use for pricing), effective effective administrationname code description myeloma multiple myelomaa 11/1/10 10/1/10-12/31/10 codescyclophosphamide J9080: cyclophosphamide, � $21.15 $11.92 96409, 96413, 96415(Cytoxan) 200 mg (all 100-mg NDCs

inactive; 500-mg NDCs used to calculate code price)

cyclophosphamide J9090: cyclophosphamide, � $52.87 $29.79 96409, 96413, 96415(Cytoxan) 500 mgcyclophosphamide J9091: cyclophosphamide, �� $95.21 $59.59 96409, 96413, 96415(Cytoxan) 1 gramcyclophosphamide J9092: cyclophosphamide, � $171.35 $119.18 96409, 96413, 96415(Cytoxan) 2 gramsdaunorubicin J9151: injection, � $68.00 $57.66 96413(DaunoXome) daunorubicin citrate,

liposomal formulation, 10 mgdexamethasone J8540: dexamethasone, �� $0.09 $0.37 N/A(Decadron) oral, 0.25 mgdexamethasone J1100: injection, � $0.15 $0.09 11900, 11901, 20600,(Decadron) dexamethasone sodium 20605, 20610, 96372,

phosphate, 1 mg 96374doxorubicin J9000: injection, � $13.20 $3.04 96409(Adriamycin) doxorubicin hydrochloride, 10 mgdoxorubicin liposomal J9001: injection, � $613.03 $486.80 96413(Doxil) doxorubicin hydrochloride,

all lipid formulations, 10 mgepirubicin J9178: injection, � $5.38 $1.80 96409, 96413(Ellence) epirubicin HCl, 2 mgetoposide J8560: etoposide, oral, � $57.33 $28.48 N/A(Vepesid) 50 mgetoposide J9181: injection, � $0.53 $0.55 96413, 96415(Etopophos, Toposar) etoposide, 10 mghydrocortisone J8499b: prescription drug, � NDC NDC N/A(Cortef) oral, non-chemotherapeutic, level level

not otherwise specified pricing pricinghydrocortisone J1720: injection, � $2.33 $3.42 96365, 96366, 96372,(Solu-Cortef) hydrocortisone sodium 96374

succinate, up to 100 mgifosfamide J9208: injection, � $42.00 $34.15 96413, 96415(Ifex) ifosfamide, 1 graminterferon alfa-2b J9214: injection, interferon, � $21.90 $16.06 96372, 96401(Intron-A) alfa-2b, recombinant,

1 million unitsinterferon alfa-n3 J9215: injection, interferon, � $25.09 None 11900, 11901(Alferon-N) alfa-n3, (human leukocyte derived), reported

250,000 international unitslomustine J8999b: prescription drug, � NDC NDC N/A(CeeNU) oral, chemotherapeutic, level level

not otherwise specified pricing pricinglomustine S0178: lomustine, � $10.59 S0178 not N/A(CeeNU) oral, 10 mg payable by

Medicaremelphalan J8600: melphalan, � $5.68 $4.80 N/A(Alkeran) oral, 2 mgmelphalan J9245: injection, melphalan � $1,922.50 $1,401.83 96409, 96413(Alkeran) hydrochloride, 50 mg






generic (Brand) HCPCS code: for multiple off-label use for pricing), effective effective administrationname code description myeloma multiple myelomaa 11/1/10 10/1/10-12/31/10 codesmethylprednisolone J1020: injection, � $3.78 $2.48 11900, 11901, 20600,(Depo-Medrol) methylprednisolone acetate, 20605, 20610, 96372

20 mg

methylprednisolone J1030: injection, � $5.22 $4.72 11900, 11901, 20600,(Depo-Medrol) methylprednisolone acetate, 20605, 20610, 96372

40 mg

methylprednisolone J1040: injection, � $9.52 $8.59 11900, 11901, 20600, (Depo-Medrol) methylprednisolone acetate, 20605, 20610, 96372

80 mg

methylprednisolone J2920: injection, � $2.36 $1.81 96365, 96366, 96372, (Solu-Medrol) methylprednisolone sodium 96374

succinate, up to 40 mg

methylprednisolone J2930: injection, � $4.15 $2.54 96365, 96366, 96372,(Solu-Medrol) methylprednisolone sodium 96374

succinate, up to 125 mg

paclitaxel J9265: injection, � $15.54 $7.45 96413, 96415(Onxol, Taxol) paclitaxel, 30 mg

peginterferon alfa-2b J3590b: unclassified biologics � NDC NDC 96372(Peg-Intron) level level

pricing pricing

peginterferon alfa-2b S0148: injection, pegylated � $116.77 S0148 not 96372(Peg-Intron) interferon alfa-2b, payable by

10 micrograms Medicare

prednisolone J7510: prednisolone, � $0.59 $0.02 N/A(Prelone, Millipred) oral, per 5 mg

prednisone J7506: prednisone, � $0.04 $0.04 N/A(Orasone, Deltasone) oral, per 5 mg

procarbazine J8999b: prescription drug, � NDC NDC N/A(Matulane) oral, chemotherapeutic, level level

not otherwise specified pricing pricing

procarbazine S0182: procarbazine HCl, � $55.68 S0182 not N/A(Matulane) oral, 50 mg payable by

Medicare

teniposide Q2017: injection, � $376.55 $323.66 96413, 96415(Vumon) teniposide, 50 mg

thalidomide J8999b: prescription drug, � NDC NDC N/A(Thalomid) oral, chemotherapeutic, level level

not otherwise specified pricing pricing

topotecan J9350: injection, � $1,348.55 $1,090.84 96413(Hycamtin) topotecan, 4 mg

vinCRIStine J9370: vincristine � $5.83 $3.98 96409(Vincasar PFS) sulfate, 1 mg



zoledronic acid J3487: injection, � $263.39 $223.10 96365, 96374(Zometa) zoledronic acid (Zometa),

1 mg




Current MedicareFDA- Compendia listed code price allowableapproved for off-label use for (AWP-based (ASP + 6%), CPT ®

generic (Brand) HCPCS code: myelodysplastic myelodysplastic pricing), effective effective administrationname code description syndromes syndromesa 11/1/10 10/1/10-12/31/10 codesamifostine J0207: injection, � $564.95 $318.66 96374(Ethyol) amifostine, 500 mgarsenic trioxide J9017: injection, � $47.51 $37.25 96413, 96415(Trisenox) arsenic trioxide, 1 mgazacitidine J9025: injection, � $6.03 $5.13 96401, 96409, 96413(Vidaza) azacitidine, 1 mgclofarabine J9027: injection, � $135.00 $115.41 96413, 96415(Clolar) clofarabine, 1 mgcytarabine J9100: injection, � $1.25 $1.98 96409, 96413, 96415,(Cytosar-U) cytarabine, 100 mg 96450cytarabine J9110: injection, � $10.20 $3.67 96409, 96413, 96415,(Cytosar-U) cytarabine, 500 mg 96450darbepoetin alfa J0881: injection, � $6.44 $2.90 96372, 96374(Aranesp) darbepoetin alfa,

1 microgram (non-ESRD use)darbepoetin alfa J0882: injection, � $6.44 $2.90 96372, 96374(Aranesp) darbepoetin alfa, 1 microgram

(for ESRD on dialysis)decitabine J0894: injection, � $35.50 $30.74 96413, 96415(Dacogen) decitabine, 1 mgepoetin alfa J0885: injection, epoetin alfa � $15.34 $9.68 96372, 96374(Procrit, Epogen) (for non-ESRD use), 1000 unitsepoetin alfa J0886: injection, epoetin alfa � $15.34 $9.68 96372, 96374(Procrit, Epogen) 1000 units (for ESRD on

dialysis; renal dialysis facilities and hospitals must use code Q4081, effective 1/1/07)

epoetin alfa Q4081: injection, epoetin � $1.53 $0.97 96372, 96374(Procrit, Epogen) alfa, 100 units (for ESRD on

dialysis; for renal dialysis facilities and hospital use)


Myelodysplastic SyndromesMyelodysplastic syndromes are a group of diseasesin which the bone marrow does not make enoughhealthy blood cells.

Associated ICD-9-CM Codes Used for Myelodysplastic Syndromes238 Neoplasm of uncertain behavior of other and unspecified sites and tissues

238.7 Other lymphatic and hematopoietic tissuesexcludes: acute myelogenous leukemia (205.0)

chronic myelomonocytic leukemia (205.1)myelosclerosis, not otherwise specified (289.89)myelosis:

not otherwise specified (205.9)megakaryocytic (207.2)

238.72 Low-grade myelodysplastic syndrome lesionsRefractory anemia (RA)Refractory anemia with ringed sideroblasts (RARS)Refractory cytopenia with multilineage dysplasia (RCMD)Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)

238.73 High-grade myelodysplastic syndrome lesionsRefractory anemia with excess blasts-1 (RAEB-1)Refractory anemia with excess blasts-2 (RAEB-2)

238.74 Myelodysplastic syndrome with 5q deletion5q minus syndrome, not otherwise specified

excludes: constitutional 5q deletion (758.39)high-grade myelodysplastic syndrome with 5q deletion (238.73)

238.75 Myelodysplastic syndrome, unspecified





Current MedicareFDA- Compendia listed code price allowableapproved for off-label use for (AWP-based (ASP + 6%), CPT ®

generic (Brand) HCPCS code: myelodysplastic myelodysplastic pricing), effective effective administrationname code description syndromes syndromesa 11/1/10 10/1/10-12/31/10 codes

etoposide J8560: etoposide, � $57.33 $28.48 N/A(Vepesid) oral, 50 mgetoposide J9181: injection, � $0.53 $0.55 96413, 96415(Toposar, Etopophos) etoposide, 10 mgfilgrastim J1440: injection, filgrastim � $283.02 $233.43 96365, 96366, 96369,(Neupogen) (G-CSF), 300 micrograms 96370, 96372, 96374filgrastim J1441: injection, filgrastim � $450.66 $366.81 96365, 96366, 96369,(Neupogen) (G-CSF), 480 micrograms 96370, 96372, 96374fludarabine J9185: injection, fludarabine � $285.16 $139.57 96413(Fludara) phosphate, 50 mgimatinib J8999b: prescription drug, � NDC NDC N/A(Gleevec) oral, chemotherapeutic, level level

not otherwise specified pricing pricingimatinib S0088: imatinib, � $48.56 S0088: not N/A(Gleevec) 100 mg payable by

Medicarelenalidomide J8999b: prescription drug, � NDC NDC N/A(Revlimid) oral, chemotherapeutic, level level

not otherwise specified pricing pricinglymphocyte immune J7504: lymphocyte immune � $643.21 $496.95 96365, 96366globulin globulin, antithymocyte globulin, (Atagam) equine, parenteral, 250 mglymphocyte J7511: lymphocyte immune � $636.48 $417.51 96365, 96366immune globulin globulin, antithymocyte globulin,(Thymoglobulin) rabbit, parenteral, 25 mgsargramostim J2820: injection, sargramostim � $44.64 $23.88 96365, 96366, 96372(Leukine) (GM-CSF), 50 microgramsthalidomide J8999b: prescription drug, oral, � NDC NDC N/A(Thalomid) chemotherapeutic, level level

not otherwise specified pricing pricingtopotecan J9350: injection, � $1,348.55 $1,090.84 96413(Hycamtin) topotecan, 4 mg

aCompendia references available upon request.bWhen billing a non-classified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for CeeNU) in Column 24D and the drug name, strength, and National DrugCode (NDC) in Box 19 to ensure appropriate reimbursement.

References

HCPCS Level II Expert, 2010 • Current Procedural Terminology (CPT®), 2010 (CPT® copyright © 2010 American Medical Association. All rights reserved. CPT® is a registered trademark of the AmericanMedical Association) • ICD-9-CM for Professionals Volumes 1 & 2, 2010 • The Drug Reimbursement Coding and Pricing Guide by RJ Health Systems International, LLC, Volume 7, Number 4, 4thQuarter 2010 • FDA-approved indication (from product’s prescribing information) • National Cancer Institute® • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC,Wethersfield, Connecticut • CMS (Centers for Medicare & Medicaid Services), Medicare Allowable 4th Quarter 2010 (effective dates: 10/1/10-12/31/10).

Prices listed herein are effective as of November 1, 2010.

ASP indicates average sales price; AWP, average wholesale price; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; FDA, US Food and Drug Administration; ESRD,end-stage renal disease; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCPCS, Healthcare Common Procedure Coding System; NDC,National Drug Code.

PO BOX 290616, Wethersfield, CT 06109 T: (860) 563-1223 • F: (860) 563-1650

www.RJHealthSystems.com

This information was supplied by:


YOU INFUSE ANTHRACYCLINES,BUT ARE YOU PREPAREDFOR AN EXTRAVASATION?

TWO PRICE OPTIONS AVAILABLE

For more information, call 866-478-8274 or visit our website at www.totect.comTo order Totect®, contact one of our authorized distributors.

ASD Healthcare(800) 746-6273

Cardinal Specialty(866) 677-4844

McKesson/OTN(800) 482-6700

Oncology Supply(800) 633-7555

US Oncology(888) 987-6679

1 Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane).Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550.2 Totect® package insert. 3 Polovich M, White JM, Olsen, M (eds.). Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (ed 3). Pittsburgh, PA, Oncology Nursing Society, 2009.4 Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R. (eds). Infusion Nurses Society Infusion Nursing an Evidence-Based Approach (ed 3). Boston, MA, Infusion Nurses Society, 2009.5 Jacobsen J., et al. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. Oncology Nursing Forum, 2009; 36:651-658.© 2010 Topotarget USA. All rights reserved. TOT0112/7-10Totect and its logo mark are registered trademarks of Topotarget A/S

First and only FDA approved treatment for anthracycline extravasation.

Supplied as a convenient and accessible complete three day treatment kit for single patient use, which should be proactively stocked on-site and infused as soon as possible andwithin 6 hours of an anthracycline extravasation.

Demonstrates 98% overall e�cacy based on two biopsy-con�rmed clinical trials1,2 inreducing or avoiding surgical intervention (i.e., surgical debridement, plastic surgery and their related costs), thereby reducing postponement of a patient’s chemotherapy treatments and the avoidance of long-term consequences.

Cited in nursing guidelines.3,4 Extravasation management is now a chemotherapy administration safety standard.5

Totect® Kit (dexrazoxane) for injection is for intravenous infusion only. Totect is indicated for the treatment of extravasation resulting from intravenous anthracycline chemotherapy.


Rx onlyTotect® is a registered trademark of Topotarget A/SUS Patent No. 6,727,253B2NDC 38423-110-01

Manufactured by:Ben Venue Laboratories, Inc.Bedford, OH 44146

Hameln Pharmaceuticals GmbH31789 HamelnGermany

Manufactured for:Topotarget A/SFruebjergvej 3DK-2100 CopenhagenDenmark

TOT0112/7-10© 2010 Topotarget USA

www.totect.com

Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Totect is a cytotoxic drug. Vial contents must be mixed and diluted before use. Totect should not be mixed or administered with any other drug during the infusion. Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasa-tion. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the �rst day. The Totect dose should be reduced 50% for patients with creati-nine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the a�ected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guide-lines on this subject have been published.3-5 Direct contact of Totect® with the skin or mucous membranes prior to and following reconstitution should be avoided. If contact occurs, wash immediately and thoroughly with water. Contraindications: None.Warnings and Precautions: Myelosuppression: treatment with Totect is asso-ciated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Use in Pregnancy: Pregnancy Category D. Totect can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions: The most common adverse reactions (≥ 16%) are nausea, pyrexia, injection site pain and vomiting.

Drug Interactions: No drug interactions have been identi�ed. Based on anecdotal reports concurrent use of topical dimethyl sulfoxide (DMSO) at the site of tissue injury may reduce the benefit of Totect. Additionally, nonclinical studies using a mouse model that simulates extravasation of anthracyclines has shown that concomitant treat-ment with topical DMSO decreases the efficacy of systemic dexrazoxane. Use in Speci�c Populations: Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. Renal Impairment: Reduce the Totect dose by 50% In patients with creatinine clearance values <40 mL/min. Pediatric Use: The safety and e�ectiveness of Totect in pediatric patients have not been established. Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Be-cause elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Overdosage: There are no data on overdosage. There is no known antidote for dexrazoxane. Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of dexrazoxane has not been investigated. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused signi�cant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m2 basis).



Breast Cancer

Prolonging Chemotherapy in Metastatic Breast Cancer Improves SurvivalBy Caroline Helwick

MILAN—Prolonging chemotherapyuntil disease progression improves pro-gression-free survival (PFS) and overallsurvival (OS) in patients with metastat-ic breast cancer (MBC), according to asystematic analysis presented at the 35thEuropean Society for Medical OncologyCongress.The findings address an important

debate in oncology, said AlessandraGennari, MD, of Ospedali Galliera inGenova. “In metastatic breast cancerthere is substantial controversy overhow long chemotherapy should be con-tinued in the absence of significant tox-icity, after the achievement of diseasecontrol,” said Gennari.Typically, the number of cycles tends

to be based on the response to treatment,symptomatic improvement, patient tol-erability and, “most importantly,” physi-cian preference, she said. “We askedwhether prolonging chemotherapy afterpatients respond or stabilize would beassociated with longer survival and timeto progression.”The investigators searched for ran-

domized trials in the first-line MBC set-

ting comparing longer and shorter du -r ations of chemotherapy. Data wereobtained from literature databases andmeeting abstracts and through contactwith individual authors of studies. Trials

comparing different types of chemo ther-apy or including high-dose chemo thera-py were excluded.Subgroup analyses were performed

according to time of randomization,type of maintenance chemotherapy,number of cycles in the shorter arm, and

whether patients received concomitantendocrine treatment.The investigators found 11 studies

involving 2269 patients to be eligible foranalysis.

Longer chemotherapy was betterPatients receiving chemotherapy of

longer duration had a 36% reduction inthe risk of progression and a 9% reduc-tion in the risk of death. “These resultsare more than clinically meaningful—they are statistically significant,” Gen -nari said at a press briefing. “The resultsjustify why we must tell patients thatthey should continue chemotherapy.”Assuming that the median OS in

MBC after first-line chemotherapy is24 months, longer chemotherapy wasassociated with absolute improvementsof about 3 months in PFS and 2months in OS.In the regression analysis, the mag-

nitude of this effect was remarkablysimilar across groups of trials, and theeffect of longer chemotherapy wasindependent of any of the factors inthe subgroup analysis.

“These results provide support to theclinical approach of prolonging first-line chemotherapy in the absence ofsignificant toxicity and disease progres-sion,” she commented.Questions remain as to the optimal

maintenance chemotherapy, such as:Should the same drug or a different onebe used? Should sequences be planned?What is the role of low-dose mainte-nance therapies? Would targeted agentsbe optimal?“Do more prolonged side effects justify

a gain of 3 months in PFS and 2 monthsof OS?” asked Miguel Martin, MD, of the Hospital Universitario Greg orioMarañón in Madrid, who discussed thepaper at the meeting. “I guess that mostpatients would accept that deal.”He said there were many caveats to

the analysis, including potential litera-ture bias. Many negative trials are neverpublished, he noted.“Even considering the caveats of the

analysis,” he concluded, “this Italianstudy provides support for the adminis-tration of chemotherapy until diseaseprogression.” �

“These results providesupport to the clinicalapproach of prolongingfirst-line chemotherapy inthe absence of significanttoxicity and diseaseprogression.”

—Alessandra Gennari, MD

SAN DIEGO—Omitting adjuvanttamo x ifen may not put women agedolder than 65 years with early-stagebreast cancer at increased risk for local ordistant disease recurrence, according to alarge, retrospective study presented at the52nd annual meeting of the AmericanSociety for Radiation On c ology.Researchers from the Cancer In stitute

of New Jersey and Yale Uni versity re -ported that women aged 65 years andolder treated with conservative surgeryand radiation therapy (CS + RT), whodid not receive adjuvant tamoxifen, didnot appear to have worse outcomes. Useof tamoxifen in this cohort did not con-fer any systemic benefit, in terms of con-tralateral breast cancer rates, systemicfailure rates, and survival rates, accordingto the investigators.Currently, adjuvant tamoxifen is

recommended for all women withestrogen receptor–positive breast car-cinoma re gardless of age. It has beenunclear, however, whether CS + RT isas effective as CS + RT plus tamox-ifen in older women with small, node-negative breast cancer.

The researchers reviewed a single-institution database of 2478 patientsand selected 224 patients aged 65 orolder who had pathologic T1 N0 M0

breast cancer treated with CS + RTbetween 1979 and 2003. The medianfollow-up time was 62.6 months. Of the224 women, 102 (45.5%) receivedtamoxifen and 122 (54.5%) did not.The researchers found that there

were four local relapses and 15 distantmetastases during the study. The 10-year local relapse-free survival was 98%in both the tamoxifen group and the notamoxifen group. The 10-year distantmetastasis-free survival was 83% in thetamoxifen group, and 89% in the notamoxifen group. Ten-year cause-specif-ic and overall survival were also statisti-cally similar in the two groups.“We found that tamoxifen did not

offer a benefit at almost every end pointwe looked at, including local control,distant control of the disease, breast can-cer–specific survival as well as overallsurvival,” said study investigator RahulParikh, MD, resident in radiation oncol-ogy at Robert Wood Johnson MedicalSchool, New Brunswick, New Jersey.“These findings held up in multivariateanalyses, and this is an expensive drugand it is not without side effects.”

Parikh said if these findings are con-firmed in other studies, it may be timeto rethink how breast cancer patients65 and older are managed. “The sideeffects of tamoxifen can include hotflashes, endometrial hyper plasia, whichcan in a small number of women lead toendometrial cancer,” he said. “So per-haps, if these women don’t benefit fromthis drug, they may not need it and theymay do well enough with adjuvant radi-ation therapy.” �

This year’s conference offers threecertifications: • Breast Patient Navigators• Clinical Breast Examiners• Breast Self-Examination Trainers, whowill be certified to teach educatorleaders who, in turn, will become certified to teach patients how to perform breast self-examination.

21st Annual NationalInterdisciplinary Breast

Center Conference

“Perhaps, if these womendon’t benefit from thisdrug, they may not need itand they may do wellenough with adjuvantradiation therapy.”

—Rahul Parikh, MD

www.breastcare.org

Tamoxifen May Confer a Limited Benefit in OlderWomen with Early-stage Breast CancerBy John Schieszer



Breast Cancer

MILAN—The investigative poly (ADP-ribose) polymerase (PARP) inhibitoriniparib (BSI-021) im proved not onlyprogression-free survival (PFS) but alsooverall survival (OS) in the finalanalysis of a randomized phase 2 study,presented at the 35th EuropeanSociety for Medical Oncology Con -gress by Joyce O’Shaughnessy, MD, ofUS Oncology and Baylor SammonsCancer Center, Houston.Co-investigator John E. Pippen,

MD, of Texas Oncology, Dallas, said ina press briefing, “These tumors are verytroublesome, as they are associatedwith high rates of symptomatic viscer-al and brain metastases. Progression-free survival is short, and median sur-vival is only about 13 months. Thereare limited treatment options.”One emerging option seems to be

agents that inhibit PARP, a keyenzyme in cell proliferation and DNArepair that is upregulated in triple-negative tumors. Iniparib and olaparibare the first two agents in this classand “may prove valuable in triple-negative breast cancer as well as othertypes of cancers,” Pippen said.The open-label study included 123

patients who received iniparib (5.6mg/kg) plus gemcitabine (1000 mg/m2)and carboplatin (AUC = 2) every 3weeks, or gemcitabine/carboplatin alone.Patients in the iniparib arm not only hada longer time to progression but also alonger survival time than patients receiv-ing only standard chemotherapy.Median OS was 12.2 months with

the combination, compared with 7.7months without iniparib, which was a43% reduction in risk (P = .014).Median PFS was 5.9 versus 3.6 months(P = .012), respectively. Objective re -sponses were observed in 52.5% of thosein the combination arm compared with32.3% of those receiving standardchemotherapy (P = .023), and the clin-ical benefit rate was 55.7% comparedwith 33.9% (P = .015), respectively,O’Shaughnessy reported.“The magnitude of survival advan-

tage is unusual in breast cancer and inmetastatic tumors in general,” sheoffered. “This may be the first therapyavailable specifically for these patientswith few options.”Most patients had three metastatic

sites of disease, and 60% had receivedno prior treatment for them.Adverse events were similar between

the arms. Grade 3/4 toxicities, whichwere primarily hematologic, were seenin 81% of patients receiving the combi-nation versus 86% of those receiving

standard chemotherapy. Serious eventsoccurred in 29% and 28% of patients,respectively. Fewer patients discontin-ued treatment because of toxicity in theiniparib arm.Commenting on the findings,

Angelo Di Leo, MD, head of Sandro

Pitigliani Medical Oncology Unit atthe Hospital of Prato, Italy, said,“Triple-negative breast cancer ac -counts for about 15% of all breastcancers, and there is a desperate needto identify effective agents for thesepatients. This trial suggests a clear

superiority of combining chemothera-py with iniparib over chemotherapyalone. Such a clear superiority is notusually observed in a trial where only123 patients have been recruited.This suggests that the drug might bevery active.” �

PARP Inhibitor Improves Survival in Triple-negativeBreast CancerBy Caroline Helwick

This activity is supported by an educational grant from Millennium Pharmaceuticals, Inc.

This activity is jointly sponsored by the University of Cincinnati, Medical Learning Institute, Inc., a nonprofit medical accreditation company, and Center of Excellence Media, LLC.

This continuing medical education symposium will serve as a forum for discussion of cur-rent questions and concerns regarding the treatment and management of patientsthrough the multiple myeloma (MM) life cycle. A panel of domestic and internationalmyeloma experts will be joined by representatives from community cancer care facili-ties and private oncology practices. By thoroughly engaging participants with interac-tive cases and physician point-counterpoint-style discussions, this symposium will provideevidence-based treatment and management recommendations and address newtreatment regimens and management strategies based on recent clinical trials andemerging data. In addition to considering differences in domestic and internationalcare, barriers and/or limitations faced by community cancer centers and private-prac-tice oncologists will be debated.

This activity has been developed for hematologists and medical oncologists, as well asnurses, pharmacists, and other allied health professionals who are interested in meetingthe challenges faced when treating patients with multiple myeloma in academic andcommunity settings.

TARGET AUDIENCE

ACKNOWLEDGMENT

At the end of this activity participants will be able to:• Apply early management strategies that consider new diagnostic and staging criteriafor SMM, MGUS, and MM and new imaging studies in order to improve prognosis foryour patients.

• Evaluate novel therapeutic regimens as induction therapy for your patients consider-ing an SCT in order to provide the most rapid response and allow the largest amountof stem cell collection, while maintaining safety and tolerance.

• Integrate novel agent-based regimens that provide optimal outcomes and a survivalbenefit into your management strategy for patients ineligible for SCT after appraisingemerging data from clinical trials.

• Identify patient- and disease-associated factors that impact choice of therapeuticagent and formulate management strategies using a risk-adapted approach to treatment of MM.

• Construct optimal treatment regimens based on novel combinations and make informed treatment decisions in order to improve the long-term outlook for myelomapatients across the life cycle of the disease.

LEARNING OBJECTIVES

PROGRAM DESCRIPTION

Leon Dragon, MD, FACPMedical DirectorKellogg Cancer CenterNorthshore University HealthSystemHighland Park, IL

Charles M. Farber, MD, PhDSection Chief of Hematology and OncologyDepartment of MedicineCarol G. Simon Cancer Center, Morristown, NJ

Shoba Kankipati, MDAssociate Physician EPIC Care East Bay Partners in Cancer CareSan Francisco Bay Area, CA

Jonathan L. Kaufman, MD Assistant Professor Blood and Marrow Transplantation Department of Hematology and Medical Oncology Emory University School of Medicine Member, Winship Cancer Institute Emory University, Atlanta, GA

Stefan Knop, MDUniversity Hospital WürzburgWürzburg, Germany

Noopur Raje, MDAssociate Professor of MedicineHarvard Medical SchoolDirector, Center for Multiple MyelomaMassachusetts General HospitalBoston, MA

G. David Roodman, MD, PhDProfessor of MedicineVice Chair for Research Department of MedicineDirector, Myeloma ProgramDirector, Bone Biology CenterUniversity of Pittsburgh Medical CenterPittsburgh, PA

Ari Umutyan, MDRedwood Regional Medical GroupHematology and Medical OncologyNapa, CA

ACCREDITATION INFORMATION Physician AccreditationThe University of Cincinnati designates this activity for a maximum of 3 AMA PRA Category1 Credits™. The University of Cincinnati is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.Physicians should only claim credit commensurate with the extent of their participationin the activity.

Registered Pharmacy DesignationMedical Learning Institute is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Completion of this activity provides for 3.0 contact hours (0.3 CEUs)of continuing education credit.

The universal activity number for this activity is 0468-9999-10-058-L01-P.

Registered Nurse DesignationMedical Learning Institute, Inc. (MLI)

Provider approved by the California Board of Registered Nursing, Provider Number15106, for 3.0 contact hours.

12:30 - 1:00 PM Registration and Lunch Service

1:00 - 1:10 PM Welcome and Introduction Sundar Jagannath, MD - Chair

CASE PRESENTATIONSEach case will be presented by an expert faculty member and discussed by the international and community panel.

1:10 – 1:40 PM Case 1: Difficult diagnosis G. David Roodman, MD, PhD

1:40 – 2:10 PM Case 2: Newly diagnosed, stem cell transplant eligible patientSundar Jagannath, MD

2:10 – 2:40 PM Case 3: First-line therapy in a non-SCT eligible patient Stefan Knop, MD

2:40 – 3:10 PM Case 4: Multiple risk factors Jonathan L. Kaufman, MD

3:10 – 3:40 PM Case 5: Treatment of MM across the life cycle Noopur Raje, MD

3:40 - 3:50 PM Question & Answer Session

3:50 - 4:00 PM Closing Remarks Sundar Jagannath, MD

PROGRAM AGENDA

CHAIR: Sundar Jagannath, MDProfessor, Hematology and Medical OncologyMount Sinai School of Medicine’s Tisch Cancer Institute Director of the Multiple Myeloma Program, The Mount Sinai Medical CenterNew York, NY

FACULTY

A Friday Satellite Symposium preceding the 52nd ASH Annual Meeting

December 3, 2010 Rosen Centre Hotel Ballrooms A & B, Orlando, Florida

Challenging Cases in MultipleMyeloma A Dialogue Between Community and Academic Clinicians to Improve Patient Care and Outcomes

Register online today atwww.myelomacases.com/register



Nursing Life

California Nurse Receives 2010ASTRO Nurse Excellence Award forPatient, Nurse EducationBy John Schieszer

SAN DIEGO—Elizabeth Brunton, RN,MSN, OCN, started in the nursing fieldin 1973. More than 35 years later, she isthe recipient of the American Societyfor Radiation Oncology (ASTRO)Nurse Excellence Award. This award ispresented annually to a registered nursewho goes above and beyond the normalstandards of nursing practice.“I really like taking care of patients.

I like being a patient advocate, and Ienjoy the teaching aspect of it,” saidBurton in an interview with TheOncology Nurse. Brunton likes to helppatients through the whole treatmentprocess and knowing that she canmake a difference in their life. She also enjoys educating nurses and

is a regular speaker at ASTRO nursemeetings as well as local OncologyNursing Society events. For her pres-entation on mucositis at ASTRO’sannual meeting in 2005, Bruntonreceived the highest evaluation ratingswithin ASTRO for that year.Brunton received her Bachelor of

Science degree in nursing from theUni versity of California, Los Angeles,and her Master of Science degree innursing from Case Western ReserveUniversity in Cleve land, Ohio. She isthe lead nurse and primary nurse in theradiation oncology department atScripps Clinic and Scripps GreenHospital in La Jolla, California, where

she has worked since 1986.In her daily role at her hospital,

Brunton is responsible for assessing thephysical, nutritional, and emotionalneeds of radiation therapy patients andassuring their optimal care. She alsomakes education a major part of hercareer. She worked across departments atScripps to develop patient educationmaterials on radiation therapy to helppatients and their families better under-stand the life-saving treatment. In 2009,she also created a patient education ori-entation program for new patients. Thecourse educates patients and their fami-lies about all aspects of radiation therapy,including physics, nursing, therapy, andsimulation. Participants are asked toevaluate the course afterward, and theresults are reported as part of Scripps’quality improvement process.Brunton also assists cancer patients

during the transition from being inactive treatment to survivorship. She ini-

tiated a procedure in the radiation oncol-ogy department to ensure that allpatients receive information regardingtheir stage, pertinent test results, and spe-cific information regarding their disease.“The nice thing about radiation ther-

apy is that there is a variety, because wetreat everything from head to toe. Wetreat some patients for cure, and wetreat some patients for palliation. Weget to see them in follow-up over time,so it is very rewarding,” said Brunton.“You really get a chance to know thepatients and their families. In a lot ofspecialties, you may see the patientonce or twice, but in our specialty, wereally get to know the patient.”Part of the key to her success has been

that she always tries to find the things ather job that she enjoys. These are thethings she stays focused on when she hasdays when her job is very difficult. “Ialways try to step out of my box and tryto learn new things,” she says. �

“I really like taking care of patients. I likebeing a patient advocate, and I enjoythe teaching aspect of it.”

—Elizabeth Brunton, RN, MSN, OCN

Roasted Salmon withPumpkin Salsa

Eating healthy can be challeng-ing during the holiday season.However, there is no reason

why a healthy meal cannot also betempting and delicious. This recipefeatures pumpkin salsa, a winter ver-sion of this popular summertime foodthat is so versatile it can be used as amain dish or a dessert. Pumpkin pro-vides an excellent source of beta-carotene, blood pressure–loweringpotassium, immune-boosting zinc,and cholesterol-reducing fiber. Pump -kin salsa can also be used as a dessert.Top a bowl of low-fat vanilla icecream with this sweet and savory salsaand make a delicious antioxidant-rich sweet treat. For even more vari-ety, replace the pumpkin with butter-nut squash.

Ingredients

1 pound pumpkin, small diced

2 cups water

1 cup brown sugar

½ cup cider vinegar

½ cup toasted walnuts

½ cup dried cranberries

1 teaspoon cinnamon

1 teaspoon allspice

1 tablespoon orange zest

Four 4-ounce portions of wild salmon

Directions

• Coat salmon with nonstick cook-ing spray and salt-free seasoning.

• Roast salmon in the oven at 400°for about 10 minutes.

• Bring water and brown sugar to aboil in a medium saucepan. Addpumpkin, and simmer for 10 min-utes or until tender. In the finalminute, add cranberries.

• Strain and toss with remainingingredients.

Serves 8: 2 ounces sauce; 4 ounces salmon

Nutritional InformationEach serving provides:320 calories, 12 g protein, 1.5 g saturated fat,60 mg cholesterol, 60 mg sodium, 28 g total carbohydrate, 2 g dietary fiber, 23 g sugars, 25 g protein

©iS

tockp

ho

to.c

om

/DN

Y5

9

RECIPE

46 December 2010 I VOL 3, NO 8

LUNG CANCER

Fast Neutron Radiotherapy May Be Safe... Continued from page 25

Among the 12 patients who hadlonger than a 1-month follow-up, sixpatients had no evidence of local can-cer progression. The median local

control of the other six patients was 3months. Nine of 14 symptomaticpatients had successful palliationwithin 1 month after treatment was

completed. The 1-year survival ratewas 20%, and 1-year disease-free sur-vival was 10%.For the study of FNRT for advanced

stage NSCLC, the researchers lookedat the results in 23 patients whoreceived a combination of FNRT andphoton radiotherapy between March

1993 and December 2006. The medianfollow-up was 5 months. No grade 4toxicities were recorded; however, threepatients developed grade 3 radiationpneumonitis. A total of 12 patientsdeveloped grade 1 or 2 esophagitis andnine patients developed grade 1 radia-tion dermatitis. One patient had grade 3radiation dermatitis.Among the 20 patients who had

longer than 1-month follow-up, 16had no evidence of local progression,and the median local control of theother four who did have recurrencewas 3 months. The median overall sur-vival was 7 months, and the mediandisease-free survival was almost 3months. One-year overall survival was32.4%, and 1-year disease-free survivalwas 5.3%. �

“Our findings are good news, and wewere happy that we did not havesimilar toxicities as have been seenin treating similar patients.”

—Andre Konski, MD, MBA


A Newsletter Series for Cancer Care Professionals

Center of Excellence Media, along with Editor-in-ChiefSagar Lonial, MD, of Emory University, are pleased tooffer your multidisciplinary cancer team this series ofnewsletters focusing on the challenges of treatingpatients with multiple myeloma.

SAGAR LONIAL, MDAssociate Professor of

Hematology and Oncology Emory University School of Medicine

� Earn Continuing Education Credits �

Each newsletter will feature:

These activities are supported by an educational grant from Millennium Pharmaceuticals, Inc.

• Front-line Therapy• Maintenance Settings• Transplant Settings• Retreatment Settings

• Non-Transplant Patients• Cytogenetics• Side Effect Management• Bone Health

• Contributions from thought-leadingphysicians, nurses, and pharmacists

• Continuing Education credits availableto physicians, nurses, and pharmacists

Presents the Third Annual Curriculum for CONSIDERATIONS IN MULTIPLE MYELOMA

PARTICIPATE TODAY at www.COEXM.com

8-part newsletter series

CASE STUDY DISCUSSIONS:

For complete learning objectives and accreditation information, please refer to each activity.

Target AudienceThese activities were developed for physicians, nurses, and pharmacists.

These activities are jointly sponsored by


��

Experts from various disciplineswill be featured in blog segments over the course of the year, allowing members tointeract with their colleagueson multiple subject areas.

Informational/educational resources to help you andyour patients navigate theircancer treatment and improve their quality of life.

Members receive subscriptions to the Journal of Oncology Navigation & Survivorship, The Oncology Nurse-APN/PA,and the bimonthly Journal of Multidisciplinary Cancer Care(a more than $150 value).

RESOURCESBLOGS

www.AONNonline.org

PUBLICATIONS

JOIN TODAY$39.95

First Year Membership�

Member Benefits Include:• Best Practices• Continuing Education• Networking • Community Resources • Publications

� �� TON_December 2010_FINAL_TON 12/6/10 11:23 AM Page 48


Meetings

adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting,and dyspnea. In Study 9, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%). In Study 10, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%). Fifty-nine percent of R-FC–treated patients experienced an infusion reaction of any severity. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human anti-chimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have beenidentified during post-approval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolongedpancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure.: Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viralinfections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneousreactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatalbronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUGINTERACTIONS Formal drug interaction studies have not been performed with Rituxan. In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Nursing Mothers It is not known whether Rituxan is secreted into human milk.However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breast-feeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL AmongLpatients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Chronic Lymphocytic LeukemiaAmong patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 Rituxan-treated patients (36%) were 65 years of age or older; of these, 100 Rituxan-treated patients (15%) were 70 years of age or older. In exploratory analyses defined by age, there was no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 70 years of age or older in Study 9 or in Study 10; there was also no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 65 years of age or older in Study 10 [see Clinical Studies]. Patients 70 years or older received lower dose intensity of fludarabine andscyclophosphamide compared to younger patients, regardless of the addition of Rituxan. In Study 9, the dose intensity of Rituxan was similar in older and younger patients, however in Study 10 older patients received a lower dose intensity of Rituxan. The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (Study 9); 56% vs. 39% (Study 10)], febrile neutropenia [16% vs. 6% (Study 9)], anemia [5% vs. 2% (Study 9); 21% vs. 10% (Study 10)], thrombocytopenia [19% vs. 8% (Study 10)], pancytopenia [7% vs. 2% (Study 9); 7% vs. 2% (Study 10)] and infections [30% vs. 14% (Study 10)]. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been administered in clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenicor mutagenic potential of Rituxan or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided theRituxan Medication Guide and provided an opportunity to read prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six months following completion of therapy. Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

Revised 02/2010 (4851501)

Jointly Marketed by:Biogen Idec Inc. 5200 Research Place San Diego, CA 92122Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990

©2010 Biogen Idec Inc. and Genentech, Inc. 7140919 February 2010

RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information.

INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) isindicated for the treatment of patients with: Relapsed or refractory, low-grade orfollicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, afterfirst-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positiveNHL in combination with CHOP or other anthracycline-based chemotherapy regimens.Chronic Lymphocytic Leukemia (CLL) Rituxan® (rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patientswith previously untreated and previously treated CD20-positive CLL. Limitations of useRituxan is not recommended for use in patients with severe, active infections.WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe,including fatal, infusion reactions. Severe reactions typically occurred during the firstinfusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions andsequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm,pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction,ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medicalmanagement (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusionreactions as needed. Depending on the severity of the infusion reaction and the requiredinterventions, temporarily or permanently discontinue Rituxan. Resume infusion at aminimum 50% reduction in rate after symptoms have resolved. Closely monitor thefollowing patients: those with pre-existing cardiac or pulmonary conditions, those whoexperienced prior cardiopulmonary adverse reactions, and those with high numbers ofcirculating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Acute renal failure,hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis,some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patientswith NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burdenconfers a greater risk of TLS. Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. Thesereactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoiddermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety ofreadministration of Rituxan to patients with severe mucocutaneous reactions has notbeen determined. [See Boxed Warning, Adverse Reactions.] Progressive MultifocalLeukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases.The majority of patients with hematologic malignancies diagnosed with PML receivedRituxan in combination with chemotherapy or as part of a hematopoietic stem celltransplant. The patients with autoimmune diseases had prior or concurrentimmunosuppressive therapy. Most cases of PML were diagnosed within 12 months oftheir last infusion of Rituxan. Consider the diagnosis of PML in any patient presentingwith new-onset neurologic manifestations. Evaluation of PML includes, but is not limitedto, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxanand consider discontinuation or reduction of any concomitant chemotherapy orimmunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologicmalignancies treated with Rituxan. The median time to the diagnosis of hepatitis wasapproximately 4 months after the initiation of Rituxan and approximately one month afterthe last dose. Screen patients at high risk of HBV infection before initiation of Rituxan.Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBVinfection for several months following Rituxan therapy. Discontinue Rituxan and anyconcomitant chemotherapy in patients who develop viral hepatitis, and instituteappropriate treatment including antiviral therapy. Insufficient data exist regarding thesafety of resuming Rituxan in patients who develop hepatitis subsequent to HBVreactivation. [See Adverse Reactions.] Infections Serious, including fatal, bacterial,fungal, and new or reactivated viral infections can occur during and up to one yearfollowing the completion of Rituxan-based therapy. New or reactivated viral infectionsincluded cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and institute appropriate anti-infective therapy. [See Adverse Reactions.] CardiovascularDiscontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxanadministration in patients with NHL. Renal toxicity has occurred in patients whoexperience tumor lysis syndrome and in patients with NHL administered concomitantcisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not anapproved treatment regimen. Monitor closely for signs of renal failure and discontinueRituxan in patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some cases leadingto death, can occur in patients receiving Rituxan in combination with chemotherapy. Inpostmarketing reports, the mean time to documented gastrointestinal perforation was 6(range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation andinstitute appropriate treatment for complaints of abdominal pain. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines followingRituxan therapy has not been studied and vaccination with live virus vaccines is notrecommended. Laboratory Monitoring In patients with lymphoid malignancies, duringtreatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse Reactions]. s Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan [see Warnings and Precautions, Adverse Reactions].s Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. s Progressive Multifocal Leukoen cephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions].s

counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy,obtain CBC and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias. [See Adverse Reactions]. The duration of cytopeniasscaused by Rituxan can extend months beyond the treatment period. ADVERSEREACTIONS The most common adverse reactions of Rituxan (incidence ≥25%)observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The most common adverse reactions of Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion reactions and neutropenia. Clinical Trials Experience in Lymphoid MalignanciesBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 2282 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1926). The population included 679 patients with low-grade follicular lymphoma, 927 patients with DLBCL, and 676 patients with CLL. Most NHL patients received Rituxan as infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination withfludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever,schills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis,occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxanwas administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL areceiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Relapsed or Refractory, Low-Grade NHL Adverse reactions in Table 1occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. [See Clinical Studies.] Most patients received Rituxan 375 mg/m2 weekly for 4 doses.Table 1Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Low-Grade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b

aAdverse reactions observed up to 12 months following Rituxan. bAdverse reactions graded for severity by NCI-CTC criteria.

In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to 6 months after Rituxan infusion. Previously Untreated Low-Grade NHL In Study 4,patients in the R-CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions were reported more frequently (≥5%) in patients receiving Rituxan following CVP compared to patients who received no furthertherapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan armcompared with those who received no further therapy (4% vs. 1%). [See Clinical Studies.] DLBCL In Studies 6 and 7, [L see Clinical Studies]s the following adverse reactions,regardless of severity, were reported more frequently (≥5%) in patients age ≥60 yearsreceiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). CLL The data below reflectexposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 patients with CLL in Study 9 or Study 10 [see Clinical Studies]. The age range was s30–83 years and 71% were men. Detailed safety data collection in Study 9 was limited to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related

All Grades (%) Grade 3 and 4 (%)

Any Adverse Events 99 57Body as a Wholey 86 10

Fever 53 1Chills 33 3Infection 31 4Asthenia 26 1Headache 19 1Abdominal Pain 14 1Pain 12 1Back Pain 10 1Throat Irritation 9 0Flushing 5 0

Heme and Lymphatic Systemy p y 67 48Lymphopenia 48 40Leukopenia 14 4Neutropenia 14 6Thrombocytopenia 12 2Anemia 8 3

Skin and Appendagespp g 44 2Night Sweats 15 1Rash 15 1Pruritus 14 1Urticaria 8 1

All Grades (%) Grade 3 and 4 (%)

Respiratory Systemp y y 38 4Increased Cough 13 1Rhinitis 12 1Bronchospasm 8 1Dyspnea 7 1Sinusitis 6 0

Metabolic and NutritionalDisorders 38 3

Angioedema 11 1Hyperglycemia 9 1Peripheral Edema 8 0LDH Increase 7 0

Digestive Systemg y 37 2Nausea 23 1Diarrhea 10 1Vomiting 10 1

Nervous Systemy 32 1Dizziness 10 1Anxiety 5 1

Musculoskeletal Systemy 26 3Myalgia 10 1Arthralgia 10 1

Cardiovascular Systemy 25 3Hypotension 10 1Hypertension 6 1

20-22 SAN FRANCISCO, CAGastrointestinal Cancers Symposiumwww.gicasymposium.org

10-12 LOS ANGELES, CA11th National Conference on CancerNursing Researchwww.ons.org

17-19 ORLANDO, FLGenitourinary Cancers Symposiumwww.gucasymposium.org

2-5 SAN ANTONIO, TXSociety of Surgical OncologyAnnual Cancer Symposiumwww.surgonc.org

9-13 HOLLYWOOD, FLNational Comprehensive CancerNetwork 16th Annual Conference:Clinical Practice Guidelines & QualityCancer Carewww.nccn.org

JANUARY 2011

12-16 LAS VEGAS, NVNational Interdisciplinary BreastCenter Conferencewww.breastcare.org

17-19 WASHINGTON, DCAssociation of Community CancerCenters Annual National Meetingwww.accc-cancer.org

Apr 28-May 1BOSTON, MA36th Oncology Nursing SocietyAnnual Congresswww.ons.org

MARCH 2011

©iS

tockp

ho

to.c

om

/Sa

m V

alte

nb

erg

s©

iSto

ckphoto

.com

/choic

egra

phx

FEBRUARY 2011

MARCH 2011

©iS

tockph

oto

.com

/Sh

an

no

n D

raw

e

APRIL 2011


ACROSS APPROVED CLL AND NHL INDICATIONS

DRIVING PATIENT OUTCOMESSupporting your central role in patient care

Resources to support your patients with NHL and CLL

Patients can talk to a nurse educator about RITUXAN, CLL, and NHL 24 hours a day, 7 days a week. Call the RITUXAN Support Center at (888) 455-2220.

You, your patients, and their caregivers can turn to RITUXAN.com for additional resources and materials.

RITUXAN Access Solutions is committed to connecting your patients to RITUXAN, regardless of their ability to pay; for more information, please visit www.RituxanAccessSolutions.com.

Warnings and Precautions RITUXAN can also result in serious, including fatal, adverse

reactions. These include hepatitis B reactivation with fulminant hepatitis and hepatic failure resulting in death; other infections, including bacterial, fungal, new or reactivated viral infections; cardiovascular events; severe, including fatal, renal toxicity; and abdominal pain, bowel obstruction and perforation, in some cases leading to death

Additional Important Safety Information The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia

The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The most frequently reported Grade 3 or 4 adverse reaction was neutropenia

In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see following page for brief summary of full prescribing information, including BOXED WARNINGS.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.

IndicationsRITUXAN® (Rituximab) is indicated for the treatment of patients with:

Previously untreated and previously treated CD20-positive CLL in combination with fl udarabine and cyclophosphamide (FC)

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent

Weekly ×4 Weekly ×8 Bulky disease Retreatment

Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy

Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy

Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens

RITUXAN is not recommended for use in patients with severe, active infections.

BOXED WARNINGS RITUXAN administration can result in serious,

including fatal, adverse reactions. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML)

©2010 Genentech USA, Inc., and Biogen Idec Inc. All rights reserved. 10026002 May 2010

Resources to support your patients pp y p

TON_December 2010_FINAL_TON 12/6/10 11:23 AM Page Cov4

December 2010, Vol 3, No 8

Documents

Transcript of December 2010, Vol 3, No 8