Anne Traynor, MDDirector, Medical Oncologist

Tracey Weigel, MDCo-Director, Thoracic Surgical Oncologist

Minesh Mehta, MDCo-Director, Thoracic Radiation Oncologist

Tien Hoang, MDMedical Oncologist

Toby Campbell, MDMedical Oncologist

Deepak Khuntia, MDRadiation Oncologist

James Maloney, MDThoracic Surgeon

J. Scott Ferguson, MD Pulmonologist

Jennifer Verhoeven, RN, MSIntegrative Medicine Specialist

Sarah Marcotte, MS, CCRPMultidisciplinary Lung Cancer Research Program Manager

Kierstyn Block, PAC

Nancy Steinhauer, PAC

UW MULTIDISCIPLINARY CANCER TEAM

Pulmonology Update

Summer 2009

As the newest member of the UW Multidis-ciplinary Lung Cancer Team, I am pleased to bring you this spring edition of “Lung Cancer Link.”

Part of the reason that the University of Wisconsin is attractive to me professionally is that there is a strong multidisciplinary lung cancer team in place with an excellent track record of clinical care and investigation. I was delighted to come here in September of 2008 in order to join this unique service and to start a program in interventional pulmonology.

My clinical practice spans all aspects of lung cancer and structural airway disorders, from prevention and screening to palliative care. However, as an interventional pulmonologist and a member of the Multidisciplinary Lung Cancer Team, my specific goal is to improve the lives of cancer patients through research and clinical applications that promote early and accurate diagnosis and staging, and through the appropriate application of interventional techniques as an adjunct for definitive and palliative treatment. In the program at UW, I believe that these aspects of research and clinical care will add to an already outstanding team.

Through the combined efforts of several individuals, the hospital, and the UW Carbone Comprehensive Cancer Center, we have recently acquired technology that will allow us to use electromagnetic guidance dur-ing bronchoscopy to investigate small lung nodules that are suspicious for cancer. As you are aware, one of the challenges in thoracic oncology is achieving an early diagnosis. With electromagnetic navigational bronchoscopy, we can approach lesions that are too small for conventional bronchoscopic evaluation. Biopsies performed with this technique may allow for an earlier diagnosis, and using a technique of pleural tattooing to mark the location of small nodules will allow for more accurate sub-lobar resections. Combined with the established programs in endobronchial

ultrasound and CT-guided needle biopsies, we believe that we will be able to offer very accu-rate minimally-in-vasive diagnostic, staging, and treat-ment strategies for patients.

All of us from the Lung Cancer Team look forward to collaborations with you. Please let us know if there is any further information you would like after reviewing “Lung Cancer Link.”

J. Scott Ferguson, MDPulmonologist

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Electromagnetic navigational bronchoscopy

Hybrid stent in airway

Images

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Our Featured Protocols

The role of systematic chemotherapy in patients with brain metastases remains limited and controversial for several reasons: • Insufficientdeliveryof chemotherapeutic agents to the CNS due to the blood-brain barrier

• Patientswithbrainmetastasesare often excluded from clinical trials

Temozolomide, is an alkylating agent that readily crosses the blood-brain barrier and reaches therapeutic concen-trations in the cerebrospinal fluid. Temozolomide has demonstrated activity in brain tumors and is cur-rently being evaluated in several studies for the treatment of brain metastases

secondary to various solid tumor types including lung cancer, breast cancer, and melanoma. In studies where temozolomide has been evaluated for the treatment of advanced NSCLC, the rate of disease progression in the brain has been very low (<10%) compared with an expected rate of ~50%. Study DesignIn this Phase II, open-label, randomized, multicenter study of maintenance temozolomide versus observation, pa-tients randomized to receive temozolomide will be administered a dose of 75 mg/m2 by mouth daily for 21 days followed by a 7-day rest period for a maximum of 6 cycles or until progression.

The primary objective of this study is to investigate whether administration of maintenance temozolomide following standard treatment could prevent or delay the onset of brain metastases in patients with controlled NSCLC.

A Randomized Phase II Study of Maintenance Temozolomide vs Observation in Stable or Responding Stage IIIB/IV Non-Small Cell Lung Cancer Patients

• InclusionCriteria:HistologicallyconfirmedNSCLC stage IIIB (with pleural and/or pericardial effusion) /IV,havereceived4-6cyclesoffirstlinesystematic therapy, and have documented CR, PR, or SD per RECIST, PS ≤2, patients on maintenance bevaci zumab are eligible

• ExclusionCriteria:Brainmetastasesdocumented on post-chemo MRI, received more than 1 anti- tumor regimen for stage IIIB/IV disease

*Select eligibility requirements

Protocol Eligibility*

Treatment for advanced, relapsed NSCLC is limited with very few choices. Preclinical and clinical studies have suggested the combination of vorinostat and bortezomib as a potential treatment for NSCLC. This study investigates this regimen further in a phase II study in NSCLC patients who have progressed through two prior systemic anti-cancer regimens.

Vorinostat, also known as suberoylanilide hydroxamic acid (SAHA; Zolinza®), is a novel agent that inhibits the enzymatic activity of histone deacetylases (HDACs). Bortezomib is a small molecule protea-some inhibitor developed by Millennium Pharmaceuticals, Inc.

The primary objective of this study is to evaluate the efficacy of vorinostat and bortezomib in the third line treatment of advanced NSCLC. Secondary objectives are to assess the toxicity, including bortezomib-induced neu-ropathy, and tolerability of this regimen in this patient population. Potential biomarkers of response such as histone acetylation, p21 and HSP70 gene expression, and 20S proteasome inhibition will also be evaluated. Study DesignThis open label phase II study of vorinos-tat and bortezomib in third-line setting of advanced NSCLC is being conducted at the University of Wisconsin and Wisconsin Oncology Network. Patients will receive

therapy until disease progression or intoler-able toxicity. Primary endpoint is 3-month PFS. Secondary endpoints include the response rate, median and overall survival, and assessment of toxicity. Bortezomib-in-duced neuropathy with patient self report questionnaires will be assessed. Correlates to investigate biomarkers of response (histone acetylation, p21 and HSP70 gene expression) will be examined from peripheral blood mononuclear cells.Patients will receive vorinostat 400 mg by mouth daily on days 1 through 14 in combination with bortezomib 1.3 mg/m2 intravenously on day 1, 4, 8, and 11 in a 21 day cycle. Tumor response will be assessed every 2 cycles.

Phase II Trial of Vorinostat (SAHA, Zolinza®) and Bortezomib (PS341, Velcade®) as Third-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer

• InclusionCriteria:Histologicallyor pathologicallyconfirmedadvancedNSCLC, have received two prior chemotherapy regimens, and have measurable disease. PS ≤ 2

• ExclusionCriteria:Priortherapywith vorinostat, other HDAC inhibitors, or bortezomib, myocardial infarction within 6 months.

*Select eligibility requirements

Protocol Eligibility*

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Our Current Protocols A complete listing of all clinical trials at the UW Carbone Cancer Center is also available on our website,www.cancer.wisc.edu.

Non-Small Cell Lung Cancer (NSCLC)

• APhaseISequentialCohort,DoseEscalationTrialtoDetermineSafety,Tolerability,andMaximumTolerateddoseofWeeklyAdministrationof GRN163LinCombinationwithPaclitaxelandCarboplatininPatientswithAdvancedorMetastaticNSCLC

• APhaseI,IntrapatientDose-EscalationStudyofSorafenibinAdvancedorRelapsedNSCLC

• APhaseIStudyofErlotinibandSunitinibinNSCLC

• APhaseIITrialofVorinostat(SAHA,Zolinza®)andBortezomib(PS341,Velcade®)asThird-LineTreatmentinPatientswithAdvancedNSCLC

• ARandomizedPhaseIIStudyofMaintenanceTemozolomideVersusObservationinStableandRespondingStageIIIB/IV Non-Small Cell Lung Cancer Patients

• PhaseIIIRandomizedTrialofAdjuvantChemotherapyWithorWithoutBevacizumabforPatientsWithCompletelyResectedStageIB ( 4cm)-IIIA Non-Small Cell Lung Cancer (ECOG 1505)

• APhaseIIIrandomized,double-blindplacebo-controlledmulti-centerstudyASA404incombinationwithpaclitaxelandcarboplatinas first-linetreatmentforlocallyadvancedormetastatic(stageIIIB-IV)non-smallcelllungcancer

• ADouble-Blind,Randomized,Placebo-ControlledPhaseIIIStudytoAssesstheEfficacyofrecMAGE-A3+AS15Antigen-SpecificCancer ImmunotherapeuticasAdjuvantTherapyinPatientswithResectableMAGE-A3-PositiveNSCLC

• APhaseIIIRandomizedTrialofLobectomyversusSublobarResectionforSmall(≤ 2 cm) Peripheral Non-Small Cell Lung Cancer

• RandomizedPhaseIIIStudyofSublobarResectionversusSublobarResectionplusBrachytherapyinHighRiskPatientswith Non-Small Cell Lung Cancer (NSCLC), 3 cm or Smaller

Small Cell Lung Cancer (SCLC)

Radiation Protocols• TheUseofHelicalTomotherapytoAchieveDose-per-fractionEscalationinLungCancer

• PhaseIStudyofImageGuidedStereotacticBodyRadiotherapyforSmallLungMalignancies

• PhaseIIITrialComparingWholeBrainRadiationandStereotacticRadiosurgeryAloneversuswithTemozolomideor Erlotinib in Patients with Non-small Cell Lung Cancer and 1 - 3 Brain Metastases

• AnOpen-label,Multi-Center,PhaseIIStudytoEvaluatetheActivityofPatupilone(EPO906),intheTreatmentofRecurrentor Progressive Brain Metastases in Patients with NSCLC

• Randomized,PhaseIII,OpenLabelStudyofOralTopotecanplusWhole-BrainRadiationTherapy(WBRT)Alonein Patients with Brain Metastases from NSCLC

• PhaseITrialofHelicalTomotherapySimultaneousBoost(SIB)TreatmentforPatientswithBrainMetastases

• PhaseIStudyEvaluationtheSafety,TolerabilityandPharmacokineticsofABT-888inCombinationwithWholeBrainRadiation TherapyinSubjectswithBrainMetastases

• ARandomized,PhaseIII,Double-Blind,Placebo-ControlledTrialofMemantineforPreventionofCognitiveDysfunctionin PatientsReceivingWholeBrainRadiotherapy

• MolecularEpidemiologyCase-SeriesStudyofNon-SmallCellLungCancerinSmokingandNonSmokingWomenandMen.

• MolecularMarkersforNon-SmallCellLungCancerSusceptibility

Chemotherapy Protocols

Radiation Protocols

Other Protocols

For more information about referring patients to the UW Paul P. Carbone Comprehensive Cancer Center, call Cancer Connect at (800) 622-8922 or (608) 262-5223.

• AnOpen-label,Multicenter,Non-comparative,PhaseIIstudyofOralTopotecaninCombinationwithBevacizumabforSecond-line TreatmentinSubjectswithRelapsedSCLC

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TogetherWe Can Save Lives

Save The Date:Inside This Issue:June 2, 2009: 2nd Annual McArdle SymposiumonCancer: Human Cancer VirusesMadison,WICall(608)262-8651 for more information

June 6, 2009: 2nd Annual Jodi Lou Lung CancerRun/WalkMadison,WIVisitjodilou.orgformoreinformation

August 10, 2009: Drive for Hope Golf TournamentOregon,WIVisitthewebsite: driveforhopemadison.com for more information

October 23, 2009: 8thAnnualSymposium:Advances in Multidisciplinary CareMadison,WICall(608)263-4982 for more information

Learn More About UW Multidisciplinary Lung Cancer Team

An Introduction to Pulmonology at UW– By J. Scott Ferguson, MD

Featured ProtocolsA Randomized Phase II Study of Mainte-nance Temozolomide vs Observation in Stable or Responding Stage IIIb/IV Non-Small Cell Lung Cancer Patients Phase II Trial of Vorinostat (SAHA, Zolin-za®) and Bortezomib (PS341, Velcade®) as Third-Line Treatment in Patients with Advanced Non-Small Cell Lung Cancer

Our Current List of Open Protocols

Lung cancer will kill:

•Morepeoplethanbreast,prostate, colon, liver, kidney, and melanoma cancers combined,

•Overthreetimesasmanymenas prostate cancer,

•Nearlytwiceasmanywomenas breast cancer,

•Anaverageof439peopleaday.

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