13© T O U C H B R I E F I N G S 2 0 0 8

Supportive Oncology

a report by

Gary H Lyman

Professor of Medicine, Division of Medical Oncology, and Director, Health Services and Outcomes Research, Duke University

Myelosuppression, including chemotherapy-induced neutropenia and

febrile neutropenia, is the major dose-limiting toxicity of cancer

chemotherapy. The myeloid colony-stimulating factors have been shown to

reduce the risk of febrile neutropenia and its complications. These agents

are available globally and are utilised worldwide in oncology practice to

support patients receiving cancer therapy. Clinical practice guidelines are

available from several international professional organisations.

Chemotherapy-induced Neutropenia

Febrile neutropenia and its complications continue to be associated

with substantial morbidity, mortality and cost.1,2 Haematological toxicity

associated with cancer chemotherapy occurs most frequently during

the initial cycles, but varies across patient populations and treatment

programmes (see Figure 1).3–5 A number of studies have also indicated

that chemotherapy-induced neutropenia is associated with improved

treatment efficacy, presumably due to the delivered chemotherapy

dose intensity.6,7 Neutropenic complications frequently result in

subsequent reductions in chemotherapy dose intensity, compromising

disease-free and overall survival in patients treated with curative

intent.8–12 Reduced chemotherapy dose intensity appears to be more

common among elderly or obese cancer patients and among certain

racial and socioeconomic subgroups.11,13–18

Risk Factors for Chemotherapy-induced

Neutropenia and Its Complications

Neutropenic complications including febrile neutropenia, infection-related

mortality and dose reductions and delays are more frequent among elderly

cancer patients receiving chemotherapy.2,17,18 While the risk of cancer

increases considerably among the elderly, increasing age is associated with

a reduced marrow reserve and more frequent co-morbid medical

conditions accompanied by declines in renal and hepatic function,

increasing the risk of treatment-related complications.19–21 Other variables

that increase the risk of neutropenic complications include the treatment

regimen and certain patient characteristics such as functional status

and medical co-morbidities. In order to more accurately predict

the risk of neutropenic complications, multivariate risk models are

undergoing extensive validation and may soon be available to assist clinical

decision-making in oncology practice (see Figure 2).22

Colony-stimulating Factors

The myeloid growth factors, and most notably granulocyte

colony-stimulating factor (G-CSF), have demonstrated the ability to

reduce the incidence and severity of neutropenia and febrile

neutropenia while improving chemotherapy dose intensity.23–26 The

long-acting myeloid growth factor pegfilgrastim appears to have several

advantages including patient convenience, improved compliance and,

potentially, greater potency.26,27 Multiple randomised controlled trials

(RCTs) have consistently shown the efficacy and safety of G-CSF, which

has recently been confirmed in a meta-analysis of RCTs in adult cancer

patients receiving cancer chemotherapy.28 Significant reductions in the

risk of febrile neutropenia were observed across studies for both solid

tumour patients and those with non-Hodgkin’s lymphoma across adult

age groups and all forms of G-CSF. Of note, a significant reduction in

the risk of febrile neutropenia was observed across a broad range of

baseline levels of risk ranging from 17 to 90%. As shown in Figure 3,

the baseline risk of febrile neutropenia in the control arms of these trials

ranges across the full spectrum of risk. In fact, a significant inverse

relationship between the baseline risk of febrile neutropenia and the

relative risk reduction with G-CSF was found (see Figure 3).28 This

analysis also demonstrated a significant reduction in infection-related

and early all-cause mortality. These observations are consistent

with that of a Cochrane meta-analysis of therapeutic CSF in

patients hospitalised with febrile neutropenia following cancer

chemotherapy.29 The meta-analysis also confirmed the ability of these

agents to sustain chemotherapy relative dose intensity averaging

95% in G-CSF patients compared with 88% in control study arms. While

few studies have been adequately powered to study overall survival or

second malignancies, no increase in mortality or risk of second

malignancies has been observed in RCTs.

Myeloid Growth Factor Use in the Elderly Cancer Patient

The risk of cancer increases with increasing age. Patients 65 years of age

and above account for some 60% of cancer diagnoses and as many as

70% of cancer deaths. Nevertheless, older patients able

to tolerate standard chemotherapy regimens and schedules appear to

derive nearly as much benefit from systemic chemotherapy as younger

cancer patients.30–32 However, clearly, increasing age is a risk factor for

Management of Chemotherapy-induced Neutropenia with Colony-stimulating Factors

Gary H Lyman is a Professor of Medicine and Director ofHealth Services and Outcomes Research in the Division ofMedical Oncology at Duke University. He is also a SeniorFellow at the Duke Center for Clinical Health Policy Researchand a member of the Duke Comprehensive Cancer Center. Hisclinical focus is on the management of early-stage breastcancer and disease and treatment-related complications. Professor Lyman serves as a member of the Oncology DrugAdvisory Committee to the US Food and Drug Administration

(FDA) on new oncological agents. He is also active within the American Society of ClinicalOncology (ASCO), serving as a member of both the Health Services and Cancer EducationCommittees, chairing the Methodology Subcommittee and leading several clinical practiceguideline panels, including the recent ASCO Guideline on The Prevention of VenousThromboembolism in Patients with Cancer. Professor Lyman has published more than 300articles and edited recent texts including Comprehensive Geriatric Oncology, TranslationalTherapeutic Strategies in Breast Cancer, Cancer Supportive Care, Advances in TherapeuticStrategies and The Oxford-American Hand Book of Oncology. Professor Lyman also serves asEditor in Chief of Cancer Investigation.

E: gary.lyman@duke.edu

Lyman_subbed.qxp 17/4/09 09:28 Page 13

14 E U R O P E A N O N C O L O G Y

Supportive Oncology

haematological toxicity, including neutropenic complications that

may result in a higher mortality in those hospitalised for febrile

neutropenia.1 Greater reductions in chemotherapy dose intensity are also

observed among elderly cancer patients with potentially compromised

disease outcome.18,33–38 However, older patients appear to be nearly as

responsive to the myeloid growth factors as younger patients.39,40 RCTs of

prophylactic myeloid growth factors in older cancer patients have

demonstrated a significant reduction in the risk of febrile

neutropenia.34,37,41 The risk of febrile neutropenia among patients 65

years of age and older is twice that of younger patients in the first cycle.4,5

Nevertheless, practice pattern studies suggest that only a minority of

elderly cancer patients receiving chemotherapy treatment receive a

myeloid growth factor, with most receiving a reduced chemotherapy

dose instead in order to reduce the risk of neutropenia.11,12,17,18

Clinical Practice Guidelines for the Myeloid Growth Factors

Clinical practice guidelines for the use of the myeloid growth factors

have been developed by various professional organisations, including

the European Organisation for Research and Treatment of Cancer

(EORTC), the National Comprehensive Cancer Network (NCCN) and

the American Society of Clinical Oncology (ASCO).13,42–44 The NCCN

guidelines differ in that they are largely based on a consensus process,

whereas the EORTC and ASCO guidelines are based on an extensive

evidence-based review (see Table 1). The various guideline panels

reviewed results from the reported RCTs and meta-analyses of these

trials. The EORTC has previously developed guidelines on the use of

these agents specifically in the elderly.35

European Organisation for Research and

Treatment of Cancer Guidelines

The EORTC guidelines for the use of G-CSF recommend routine

prophylactic use of G-CSF in those receiving a regimen with a 20% or

greater risk of febrile neutropenia.42 The guidelines recommend an

individual risk assessment in those receiving a regimen associated with

a risk of between 10 and 20%, but advise against routine growth

factor use when the risk is less than 10% (see Figure 4). Likewise,

prophylactic G-CSF is recommended when dose-dense or dose-intense

chemotherapy has been shown to have survival benefit. Finally, where

a reduction in chemotherapy dose intensity may be associated with a

poor outcome, consideration of G-CSF prophylaxis to maintain dose

intensity is recommended.

National Comprehensive Cancer Network Guidelines

The myeloid growth factor guidelines from the NCCN have been updated

annually since their generation in 2005.13,45 After an initial evaluation

Figure 1: Risk of Neutropenic Complications in the First Cycle of Chemotherapy

00 20 40 60 80 100 120

0.5

1.0

1.5

2.0

2.5

Days to first febrile neutropenia episode

Haza

rd ra

te

0

20

40

60

80

100

Breastcancer

Non-small-cell lungcancer

Small-celllung cancer

Colorectalcancer

Non-Hodgkin’slymphoma

Hodgkin’sdisease

Ovariancancer

58.4

73.5

5057.4

71.474.2 62.5

52.8

61.557.1

54.5

46.076.580

FNFN or SN

Even

ts in

cyc

le I,

% (9

5% C

I)

Risk of neutropenic events in patients receiving cancer chemotherapy is greatest in the firstcycle of treatment. A hazard plot for the initial episode of febrile neutropenia is shown froma study of patients with non-Hodgkin’s lymphoma receiving cyclophosphamide, doxorubicin,prednisone, vincristine (CHOP) chemotherapy.5 The bar graph represents the proportion(±95% confidence interval [CI]) of febrile neutropenia (blue bars) and severe or febrileneutropenia (purple bars) occurring in the first cycle of chemotherapy across several cancertypes from a large US prospective observational study.3

FN = febrile neutropenia; SN = severe neutropenia.

Figure 2: The Course of Neutropenia and Its Complications

Pre-treatment bloodcell counts

Lymphocyte counts

Haemoglobin level

Lactatedehydrogenase level

Bone marrowinvolvement

Neutrophil count

Prolonged neutropenia

Monocyte count

Platelet count

Blood urea nitrogen level

Glucose level

Lactatedehydrogenase level

Burden of illness

Age

Female sex

Performance status

Nutrition

Body surface area

Temperature

Blood pressure

Infection atintravenous site

Pneumonia

Antifungalprophylaxis

No antibiotics

Chemotherapy intensity

Neutropenia

Febrile neutropenia

Complicated infectionBacteraemia

Prolonged hospitalisation

Death

Figure 3: The Baseline Risk of Febrile Neutropenia in the ControlArms of Randomised Trials Included in the Recent Meta-analysisRanges Across the Full Spectrum of Risk

0.00.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

0.2

0.4

0.6

0.8

1.0

Control risk of FN

Rela

tive

risk

redu

ctio

n of

FN

A significant inverse relationship was observed between the baseline risk of febrileneutropenia (FN) and the relative risk reduction with granulocyte colony-stimulating factor(G-CSF) across studies.28

Lyman_subbed.qxp 17/4/09 09:29 Page 14

15

based on the type of cancer, chemotherapy regimen, patient-specific risk

factors and treatment intention, a formal risk assessment is encouraged

(see Figure 5). Like the EORTC guidelines, the NCCN guidelines

recommend the use of G-CSF prophylaxis in cancer patients at 20% or

greater risk of febrile neutropenia. If there are additional risk factors that

place the patient at greater risk of febrile neutropenia or serious

consequences, those receiving an intermediate-risk regimen in the range

of 10–20% may be offered prophylactic G-CSF. The NCCN guidelines also

recommend the use of CSFs to sustain or maintain treatment intensity in

those with curable cancers.

American Society of Clinical Oncology Guidelines

While the original ASCO guidelines for the CSFs were published in 1994,

the updated 2006 ASCO White Blood Cell Growth Factor Guideline also

recommends the use of CSF prophylaxis when risk is approximately 20%

or greater.44 Likewise, these agents are encouraged when special

circumstances such as older age, co-morbid illnesses, previous febrile

neutropenia and other risk factors for serious infection place a patient at

an increased risk of febrile neutropenia and an equally effective regimen

is not available. The principal evidence for the efficacy of the myeloid

growth factors considered was based on the results of multiple RCTs and

the recent meta-analysis of 17 RCTs of prophylactic G-CSF.28 Derivative

products available with the guidelines include executive and patient

summaries, a PowerPoint slide set and a worksheet to assist

dissemination and application of the guidelines. These have been

generated and are available at the ASCO website (www.asco.org).

A comparison of the three guidelines based on a critical appraisal has

recently been reported.43 Specific clinical content areas were extracted

from each guideline and the comparative quality of the guidelines

evaluated. While the NCCN guidelines are more concise and

practical, the EORTC and ASCO guidelines were more rigorous. The

recommendations from these guidelines are remarkably consistent for both

primary and secondary prophylaxis with the CSFs. The guidelines are also

similar in recommending consideration of their use in the elderly, sustaining

chemotherapy dose intensity and individualised risk assessment based on

patient-specific risk factors such as previous febrile neutropenia, prior

chemotherapy, advanced stage, age of 65 years or above, poor

performance, nutritional status, co-morbidities and low baseline blood

counts. The quality of the guidelines is generally very good, with little

difference in issues related to the scope and purpose, stakeholder

involvement and applicability of the guidelines.40,43 The NCCN guidelines

undergo a more explicit and thorough independent and external review.

The ASCO and EORTC guidelines state individual panel member conflicts of

interest, whereas the NCCN guidelines only reflect general potential panel

conflicts. On the other hand, the NCCN guidelines are updated annually

and the use of algorithms is helpful for comprehension and application.

Cost and the Use of the Myeloid Growth Factors

The decision of whether to use a CSF in chemotherapy patients should

be based primarily on clinical indications guided by the

recommendations discussed above. However, the cost of the myeloid

growth factors raises economic considerations at the societal level that

should be balanced against the reduction in costs of hospitalisation,

any reduction in early mortality from infection and the potential effect

of chemotherapy dose intensity on patient survival. The cost of

hospitalisation for febrile neutropenia varies considerably, ranging

from US$10,000 to US$20,000 per episode in most US studies.1,46,47

Economic analyses based on the efficacy demonstrated in RCTs and

the trade-off between costs of growth factor use and the reduction in

risk or duration of febrile neutropenia have provided estimates of

overall treatment costs.48,49

While the results of these studies have not had a direct influence on

the recommendations provided by clinical practice guidelines, the

Figure 4: European Organisation for Research and Treatment ofCancer Patient Assessment Algorithm to Decide ProphylacticGranulocyte Colony-stimulating Factor Usage

Step 1Assess frequency of FN associated with the planned chemotherapy regimen

Step 2Assess factors that increase the frequency/risk of FN

Step 3Define the patient’s overall FN risk for planned chemotherapy regimen

FN risk >20%

Overall FN risk >20%

Prophylactic G-CSF recommended G-CSF use not indicated

Overall FN risk <20%

High risk Age >65 years

Increased risk Advanced disease(level I and II evidence) History of prior FN No antibiotic prophylaxis, no G-CSF use

Other factors Poor performance and/or nutritional status(level III and IV evidence) Female gender Haemoglobin <12g/dl Liver, renal or cardiovascular disease

FN risk <10%FN risk 10–20%

G-CSF = granulocyte colony-stimulating factor; FN = febrile neutropenia.Source: Aapro et al., 2006.42

Figure 5: National Comprehensive Cancer Network Guidelines –Decision Tree for Primary Prophylaxis

1. Evaluate 2. Assess risk 3. Intervene

DiseaseUse G-CSF

Chemotherapyregimen

Consider G-CSF

No routine G-CSF

Patient riskfactors

Treatment intent

High(<20%) risk

Intermediate(10–20%) risk

Low(<10%) risk

G-CSF = granulocyte colony-stimulating factor.Source: Lyman, 2005.45

E U R O P E A N O N C O L O G Y

Management of Chemotherapy-induced Neutropenia with Colony-stimulating Factors

Table 1: Critical Appraisal of Myeloid Growth Factor Guidelines

ASCO 2006 (%) EORTC (%) NCCN (%)Category Domain ScoreScope and purpose 100 100 100

Stakeholder involvement 42 50 42

Rigor of development 76 76 48

Clarity and presentation 92 83 100

Applicability 67 67 67

Editorial independence 67 67 33

Modified from Lyman GH, 2007.40

Lyman_subbed.qxp 22/5/09 09:41 Page 15

16 E U R O P E A N O N C O L O G Y

Supportive Oncology

economic analyses have demonstrated that prophylactic myeloid

growth factor use may reduce costs in many clinical settings. A recent

study has estimated a net cost saving with primary prophylaxis with G-

CSF at a threshold risk of febrile neutropenia of 20% or greater based

on average US direct medical costs for hospitalisation for febrile

neutropenia.48 The addition of indirect and out-of-pocket costs with

febrile neutropenia to the analysis results in greater net cost savings

with myeloid growth factors.50 The use of the myeloid growth factors

used at the time of hospitalisation for febrile neutropenia may result in

further cost savings by reducing the length of hospitalisation.50 Recent

studies have demonstrated the potential clinical and economic value of

targeting the myeloid growth factors towards patients at greatest risk

based on accurate and valid predictive models.22

Conclusions

Prophylaxis with the colony-stimulating agents represents an effective and

reasonably cost-effective method to reduce the risk of febrile neutropenia

in patients receiving cancer chemotherapy. Guidelines for the use of the

myeloid growth factors from major professional organisations support

their use when the risk of febrile neutropenia is 20% or greater and in a

number of special circumstances, including the elderly or those with

serious co-morbidities.

While indications for the appropriate use of these agents have expanded,

continued monitoring for any safety signals is essential. Efforts to define

better strategies for identifying patients who are at an increased risk and are

most likely to benefit from myeloid growth factor support are under way. ■

1. Kuderer NM, Dale DC, Crawford J, et al., Mortality, morbidity,and cost associated with febrile neutropenia in adult cancerpatients, Cancer, 2006;106:2258–66.

2. Lyman GH, Kuderer NM, Epidemiology of febrile neutropenia,Support Cancer Ther, 2003;1:1–12.

3. Crawford J, Dale DC, Kuderer NM, et al., Risk and timing ofneutropenic events in adult cancer patients receivingchemotherapy: the results of a prospective nationwide study ofoncology practice, J Natl Compr Canc Netw, 2008l6:109–18.

4. Lyman GH, Delgado DJ, Risk and timing of hospitalization forfebrile neutropenia in patients receiving CHOP, CHOP-R, orCNOP chemotherapy for intermediate-grade non-Hodgkinlymphoma, Cancer, 2003;98:2402–9.

5. Lyman GH, Morrison VA, Dale DC, et al., Risk of febrileneutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy, LeukLymphoma, 2003;44:2069–76.

6. Di Maio M, Gridelli C, Gallo C, et al., Chemotherapy-inducedneutropenia and treatment efficacy in advanced non-small-celllung cancer: a pooled analysis of three randomised trials, LancetOncol, 2005;6:669–77.

7. Crawford J, Armitage J, Balducci L et al: Myeloid growthfactors. J Natl Compr Netw, 2009; 7: 64-83.

8. Bonneterre J, Roche H, Kerbrat P, et al., Epirubicin increaseslong-term survival in adjuvant chemotherapy of patients withpoor-prognosis, node-positive, early breast cancer: 10-yearfollow-up results of the French Adjuvant Study Group 05randomized trial, J Clin Oncol, 2005’23:2686–93.

9. Budman DR, Berry DA, Cirrincione CT, et al., Dose and doseintensity as determinants of outcome in the adjuvant treatmentof breast cancer. The Cancer and Leukemia Group B, J NatlCancer Inst, 1998;90:1205–11.

10. Chu E, DeVita V., Principles of Medical Oncology, 7th Edition,Philadelphia: Lippincott, 2006.

11. Lyman GH, Dale DC, Crawford J, Incidence and predictors oflow dose-intensity in adjuvant breast cancer chemotherapy: anationwide study of community practices, J Clin Oncol,2003;21:4524–31.

12. Lyman GH, Dale DC, Friedberg J, et al., Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study, J Clin Oncol,2004;22:4302–11.

13. Crawford J, Althaus B, Armitage J, et al., Myeloid growthfactors. Clinical practice guidelines in oncology, J Natl ComprCanc Netw, 2007;5:188–202.

14. Griggs JJ, Culakova E, Sorbero ME, et al., Social and racialdifferences in selection of breast cancer adjuvant chemotherapyregimens, J Clin Oncol, 2007;25:2522–7.

15. Griggs JJ, Culakova E, Sorbero ME, et al., Effect of patientsocioeconomic status and body mass index on the quality ofbreast cancer adjuvant chemotherapy, J Clin Oncol, 2007;25:277–84.

16. Griggs JJ, Sorbero ME, Lyman GH, Undertreatment of obesewomen receiving breast cancer chemotherapy, Arch Intern Med,2005;165:1267–73.

17. Shayne M, Crawford J, Dale DC, et al., Predictors of reduceddose intensity in patients with early-stage breast cancerreceiving adjuvant chemotherapy, Breast Cancer Res Treat,2006;100:255–62.

18. Shayne M, Culakova E, Poniewierski MS, et al., Dose intensity

and hematologic toxicity in older cancer patients receivingsystemic chemotherapy, Cancer, 2007;110:1611–20.

19. Balducci L, Hardy CL, Anemia of Aging: A Model ofErythropoiesis in Cancer Patients, Cancer Control, 1998;5:17–21.

20. Balducci L, Hardy CL, Lyman GH, Hemopoiesis and aging,Cancer Treat Res, 2005;124:109–34.

21. Balducci L, Yates J, General guidelines for the management ofolder patients with cancer, Oncology, 2000;14:221–7.

22. Lyman GH, Lyman CH, Agboola O, Risk models for predictingchemotherapy-induced neutropenia, Oncologist, 2005;10:427–37.

23. Crawford J, Ozer H, Stoller R, et al., Reduction by granulocytecolony-stimulating factor of fever and neutropenia induced bychemotherapy in patients with small-cell lung cancer, N Engl JMed, 1991325:164–70.

24. Trillet-Lenoir V, Green J, Manegold C, et al., Recombinantgranulocyte colony stimulating factor reduces the infectiouscomplications of cytotoxic chemotherapy, Eur J Cancer,1993;29A:319–24.

25. Komrokji RS, Lyman GH, The colony-stimulating factors: use toprevent and treat neutropenia and its complications, ExpertOpin Biol Ther, 2004;4:1897–1910

26. Lyman GH, Pegfilgrastim: a granulocyte colony-stimulatingfactor with sustained duration of action, Expert Opin Biol Ther,2005;5:1635–46.

27. Pinto L, Liu Z, Doan Q, et al., Comparison of pegfilgrastim withfilgrastim on febrile neutropenia, grade IV neutropenia andbone pain: a meta-analysis of randomized controlled trials, CurrMed Res Opin, 2007;23:2283–95.

28. Kuderer NM, Dale DC, Crawford J, et al., Impact of primaryprophylaxis with granulocyte colony-stimulating factor on febrileneutropenia and mortality in adult cancer patients receivingchemotherapy: a systematic review, J Clin Oncol, 2007;25:3158-67.

29. Clark OA, Lyman GH, Castro AA, et al., Colony-stimulatingfactors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials, J Clin Oncol,2005;23:4198–214.

30. Elkin EB, Hurria A, Mitra N, et al., Adjuvant chemotherapy andsurvival in older women with hormone receptor-negative breastcancer: assessing outcome in a population-based, observationalcohort, J Clin Oncol, 2006;24:2757–64.

31. Giordano SH, Duan Z, Kuo YF, et al., Use and outcomes ofadjuvant chemotherapy in older women with breast cancer, J Clin Oncol, 2006;24:2750–56.

32. Sargent DJ, Goldberg RM, Jacobson SD, et al., A pooledanalysis of adjuvant chemotherapy for resected colon cancer inelderly patients, N Engl J Med, 2001;345:1091–7.

33. Morrison VA, Picozzi V, Scott S, et al., The impact of age ondelivered dose intensity and hospitalizations for febrileneutropenia in patients with intermediate-grade non-Hodgkin’slymphoma receiving initial CHOP chemotherapy: a risk factoranalysis, Clin Lymphoma, 2001;2:47–56.

34. Osby E, Hagberg H, Kvaloy S, et al., CHOP is superior to CNOPin elderly patients with aggressive lymphoma while outcome isunaffected by filgrastim treatment: results of a NordicLymphoma Group randomized trial, Blood, 2003;101:3840–48.

35. Repetto L, Biganzoli L, Koehne CH, et al., EORTC Cancer in theElderly Task Force guidelines for the use of colony-stimulating

factors in elderly patients with cancer, Eur J Cancer, 2003;39:2264–72.

36. Rossini F, Prognosis of infections in elderly patients withhaematological diseases, Support Care Cancer, 1996;4:46–50.

37. Zinzani PL, Storti S, Zaccaria A, et al., Elderly aggressive-histology non-Hodgkin’s lymphoma: first-lineVNCOP-B regimen experience on 350 patients, Blood, 1999;94:33–8.

38. Crivellari D, Bonetti M, Castiglione-Gertsch M, et al., Burdensand benefits of adjuvant cyclophosphamide, methotrexate, andfluorouracil and tamoxifen for elderly patients with breastcancer: the International Breast Cancer Study Group Trial VII, J Clin Oncol, 2000;18:1412–22.

39. Chatta GS, Price TH, Allen RC, et al., Effects of in vivorecombinant methionyl human granulocyte colony-stimulatingfactor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adultvolunteers, Blood, 1994;84:2923–9.

40. Shank WA Jr, Balducci L, Recombinant hemopoietic growthfactors: comparative hemopoietic response in younger and oldersubjects, J Am Geriatr Soc, 1992;40:151–4.

41. Doorduijn JK, van der Holt B, van Imhoff GW, et al., CHOPcompared with CHOP plus granulocyte colony-stimulating factorin elderly patients with aggressive non-Hodgkin’s lymphoma, J Clin Oncol, 2003;21:3041–50.

42. Aapro MS, Cameron DA, Pettengell R, et al., EORTC guidelinesfor the use of granulocyte-colony stimulating factor to reducethe incidence of chemotherapy-induced febrile neutropenia inadult patients with lymphomas and solid tumours, Eur J Cancer,2006;42:2433–53.

43. Lyman GH, Kleiner JM, Summary and comparison of myeloidgrowth factor guidelines in patients receiving cancerchemotherapy, J Natl Compr Canc Netw, 2007;5:217–28.

44. Smith TJ, Khatcheressian J, Lyman GH, et a., 2006 update ofrecommendations for the use of white blood cell growthfactors: an evidence-based clinical practice guideline, J ClinOncol, 24:3187-205, 2006

45. Lyman GH, Guidelines of the National Comprehensive CancerNetwork on the use of myeloid growth factors with cancerchemotherapy: a review of the evidence, J Natl Compr CancNetw, 2005;3:557–71.

46. Lyman GH, Kuderer N, Greene J, et al., The economics of febrileneutropenia: implications for the use of colony-stimulatingfactors, Eur J Cancer, 1998;34:1857–64.

47. Lyman GH, Kuderer NM, The economics of the colony-stimulating factors in the prevention and treatment offebrile neutropenia, Crit Rev Oncol Hematol, 2004;50:129–46.

48. Eldar-Lissai A, Cosler LE, Culakova E, et al., Economic analysisof prophylactic pegfilgrastim in adult cancer patients receivingchemotherapy, Value Health, 2001;11:172–9.

49. Lyman GH, Lyman CG, Sanderson RA, et al., Decision analysisof hematopoietic growth factor use in patients receiving cancerchemotherapy, J Natl Cancer Inst, 1993;85:488–93.

50. Cosler LE, Calhoun EA, Agboola O, et al., Effects of indirect andadditional direct costs on the risk threshold for prophylaxis withcolony-stimulating factors in patients at risk for severeneutropenia from cancer chemotherapy, Pharmacotherapy,2004;24:488–94.

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European Oncology Nursing

Society (EONS)

INTRODUCTION

The European Oncology Nursing Society (EONS) has provided supportto cancer nurses across Europe since 1984.The mission of EONS is toadd value to the work of its individual members and national societiesin delivering care to patients with cancer. It aims to assist in the pro-motion of healthy communities through influencing, research and edu-cation.

The changing landscape of cancer management in relation to cancertreatments, new technologies, psychosocial care and health care provi-sion has meant a significant shift in the way nurses apply their clinicalskills and knowledge in the workplace. However, the professional devel-opment and status of cancer nurses across Europe is not uniform andEONS strategic agenda (CARE) aims to address this inequality byworking with oncology nurses through their national societies.

STRATEGIC PRIORITIES

CommunicationCommunicating with and to oncology nurses across Europe remainsa challenge. Developing diverse communication pathways is complexand EONS is committed to doing this by continuing to produce anddistribute (through the national societies) a newsletter four timesa year.The EONS website (part of Cancerworld) is an establishedforum for cancer nurses and EONS will be developing multi-languagesections within the site as well as options for interactive forums topromote professional discussion, information and networking.TheEuropean Journal of Oncology Nursing continues to be one of theleading cancer journals and celebrated 10 years of publication in 2006.

Political Agenda EONS is one of the professional cancer societies that form part of theumbrella organisation renamed ECCO in 2007 (European CanCerOrganisation) previously known as FECS – Federation of European CancerSocieties.The organisation provides a collective political voice in Europe.EONS is also a member of the European Specialist Nurses Organisation(ESNO) which consists of associations from both European NursingSpecialist and Nursing Interest Groups.The organisation acts as a platformto represent nursing in the wider political forum.

Research Promoting evidence based clinical practice through research hasalways been a core function of EONS.Various grants are distributedthrough EONS to promote and facilitate research initiatives. Oneof the priorities is to develop a European cancer nursing researchnetwork which will enable wider collaboration, participation andsharing of research evidence as well as build a body of research anddevelopment expertise.

EducationThe themes as priorities in education are to develop cancer nurseeducators to develop and accredit teaching programmes which haveeducation quality standards as part of the review process. Inequalityin accessing post-registration cancer nursing education exists acrossEurope.Alongside this work is the commitment to develop specialisteducation and leadership programmes which can be viewed inwww.cancerworld.org/eons

Notwithstanding the busy agenda the patient experience lies at theheart of the CARE Strategy. By utilising and working in collaborationwith patients, EONS will continue to provide a unique contributionto the agenda of cancer care in Europe, whilst promoting the uniquecontribution of cancer nursing in this processs.

For more information on EONS, please contact the secretariat at

eons.secretariat@skynet.be

CARE encompasses fourbodies of work:

C Communication

A Activities for the Political agenda

R Research

E Education

EONS_ad.qxp 17/4/09 09:32 Page 17