neutropenia management

1. 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 of
Health Services and Outcomes Research in the Division of
Medical Oncology at Duke University. He is also a Senior
Fellow at the Duke Center for Clinical Health Policy Research
and a member of the Duke Comprehensive Cancer Center. His
clinical focus is on the management of early-stage breast
cancer and disease and treatment-related complications.
Professor Lyman serves as a member of the Oncology Drug
Advisory Committee to the US Food and Drug Administration
(FDA) on new oncological agents. He is also active within the American Society of Clinical
Oncology (ASCO), serving as a member of both the Health Services and Cancer Education
Committees, chairing the Methodology Subcommittee and leading several clinical practice
guideline panels, including the recent ASCO Guideline on The Prevention of Venous
Thromboembolism in Patients with Cancer. Professor Lyman has published more than 300
articles and edited recent texts including Comprehensive Geriatric Oncology, Translational
Therapeutic Strategies in Breast Cancer, Cancer Supportive Care, Advances in Therapeutic
Strategies and The Oxford-American Hand Book of Oncology. Professor Lyman also serves as
Editor in Chief of Cancer Investigation.
E: gary.lyman@duke.edu
Lyman_subbed.qxp 17/4/09 09:28 Page 13

2. 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
0
0 20 40 60 80 100 120
0.5
1.0
1.5
2.0
2.5
Days to first febrile neutropenia episode
Hazardrate
0
20
40
60
80
100
Breast
cancer
Non-small-
cell lung
cancer
Small-cell
lung cancer
Colorectal
cancer
Non-Hodgkin’s
lymphoma
Hodgkin’s
disease
Ovarian
cancer
58.4
73.5
50
57.4
71.4
74.2 62.5
52.8
61.5
57.1
54.5
46.076.5
80
FN
FN or SN
EventsincycleI,%(95%CI)
Risk of neutropenic events in patients receiving cancer chemotherapy is greatest in the first
cycle of treatment. A hazard plot for the initial episode of febrile neutropenia is shown from
a 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 febrile
neutropenia (purple bars) occurring in the first cycle of chemotherapy across several cancer
types 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 blood
cell counts
Lymphocyte counts
Haemoglobin level
Lactate
dehydrogenase level
Bone marrow
involvement
Neutrophil count
Prolonged neutropenia
Monocyte count
Platelet count
Blood urea nitrogen level
Glucose level
Lactate
dehydrogenase level
Burden of illness
Age
Female sex
Performance status
Nutrition
Body surface area
Temperature
Blood pressure
Infection at
intravenous site
Pneumonia
Antifungal
prophylaxis
No antibiotics
Chemotherapy intensity
Neutropenia
Febrile neutropenia
Complicated infection
Bacteraemia
Prolonged hospitalisation
Death
Figure 3: The Baseline Risk of Febrile Neutropenia in the Control
Arms of Randomised Trials Included in the Recent Meta-analysis
Ranges Across the Full Spectrum of Risk
0.0
0.1 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
RelativeriskreductionofFN
A significant inverse relationship was observed between the baseline risk of febrile
neutropenia (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

3. 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 of
Cancer Patient Assessment Algorithm to Decide Prophylactic
Granulocyte Colony-stimulating Factor Usage
Step 1
Assess frequency of FN associated with the planned chemotherapy regimen
Step 2
Assess factors that increase the frequency/risk of FN
Step 3
Define 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
Disease
Use G-CSF
Chemotherapy
regimen
Consider G-CSF
No routine G-CSF
Patient risk
factors
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 Score
Scope 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

4. 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 cancer
patients, 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 of
neutropenic events in adult cancer patients receiving
chemotherapy: the results of a prospective nationwide study of
oncology practice, J Natl Compr Canc Netw, 2008l6:109–18.
4. Lyman GH, Delgado DJ, Risk and timing of hospitalization for
febrile neutropenia in patients receiving CHOP, CHOP-R, or
CNOP chemotherapy for intermediate-grade non-Hodgkin
lymphoma, Cancer, 2003;98:2402–9.
5. Lyman GH, Morrison VA, Dale DC, et al., Risk of febrile
neutropenia among patients with intermediate-grade
non-Hodgkin’s lymphoma receiving CHOP chemotherapy, Leuk
Lymphoma, 2003;44:2069–76.
6. Di Maio M, Gridelli C, Gallo C, et al., Chemotherapy-induced
neutropenia and treatment efficacy in advanced non-small-cell
lung cancer: a pooled analysis of three randomised trials, Lancet
Oncol, 2005;6:669–77.
7. Crawford J, Armitage J, Balducci L et al: Myeloid growth
factors. J Natl Compr Netw, 2009; 7: 64-83.
8. Bonneterre J, Roche H, Kerbrat P, et al., Epirubicin increases
long-term survival in adjuvant chemotherapy of patients with
poor-prognosis, node-positive, early breast cancer: 10-year
follow-up results of the French Adjuvant Study Group 05
randomized trial, J Clin Oncol, 2005’23:2686–93.
9. Budman DR, Berry DA, Cirrincione CT, et al., Dose and dose
intensity as determinants of outcome in the adjuvant treatment
of breast cancer. The Cancer and Leukemia Group B, J Natl
Cancer 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 of
low dose-intensity in adjuvant breast cancer chemotherapy: a
nationwide 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 growth
factors. Clinical practice guidelines in oncology, J Natl Compr
Canc Netw, 2007;5:188–202.
14. Griggs JJ, Culakova E, Sorbero ME, et al., Social and racial
differences in selection of breast cancer adjuvant chemotherapy
regimens, J Clin Oncol, 2007;25:2522–7.
15. Griggs JJ, Culakova E, Sorbero ME, et al., Effect of patient
socioeconomic status and body mass index on the quality of
breast cancer adjuvant chemotherapy, J Clin Oncol, 2007;25:
277–84.
16. Griggs JJ, Sorbero ME, Lyman GH, Undertreatment of obese
women receiving breast cancer chemotherapy, Arch Intern Med,
2005;165:1267–73.
17. Shayne M, Crawford J, Dale DC, et al., Predictors of reduced
dose intensity in patients with early-stage breast cancer
receiving 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 receiving
systemic chemotherapy, Cancer, 2007;110:1611–20.
19. Balducci L, Hardy CL, Anemia of Aging: A Model of
Erythropoiesis 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 of
older patients with cancer, Oncology, 2000;14:221–7.
22. Lyman GH, Lyman CH, Agboola O, Risk models for predicting
chemotherapy-induced neutropenia, Oncologist, 2005;10:
427–37.
23. Crawford J, Ozer H, Stoller R, et al., Reduction by granulocyte
colony-stimulating factor of fever and neutropenia induced by
chemotherapy in patients with small-cell lung cancer, N Engl J
Med, 1991325:164–70.
24. Trillet-Lenoir V, Green J, Manegold C, et al., Recombinant
granulocyte colony stimulating factor reduces the infectious
complications of cytotoxic chemotherapy, Eur J Cancer,
1993;29A:319–24.
25. Komrokji RS, Lyman GH, The colony-stimulating factors: use to
prevent and treat neutropenia and its complications, Expert
Opin Biol Ther, 2004;4:1897–1910
26. Lyman GH, Pegfilgrastim: a granulocyte colony-stimulating
factor 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 with
filgrastim on febrile neutropenia, grade IV neutropenia and
bone pain: a meta-analysis of randomized controlled trials, Curr
Med Res Opin, 2007;23:2283–95.
28. Kuderer NM, Dale DC, Crawford J, et al., Impact of primary
prophylaxis with granulocyte colony-stimulating factor on febrile
neutropenia and mortality in adult cancer patients receiving
chemotherapy: a systematic review, J Clin Oncol, 2007;25:
3158-67.
29. Clark OA, Lyman GH, Castro AA, et al., Colony-stimulating
factors 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 and
survival in older women with hormone receptor-negative breast
cancer: assessing outcome in a population-based, observational
cohort, J Clin Oncol, 2006;24:2757–64.
31. Giordano SH, Duan Z, Kuo YF, et al., Use and outcomes of
adjuvant chemotherapy in older women with breast cancer,
J Clin Oncol, 2006;24:2750–56.
32. Sargent DJ, Goldberg RM, Jacobson SD, et al., A pooled
analysis of adjuvant chemotherapy for resected colon cancer in
elderly patients, N Engl J Med, 2001;345:1091–7.
33. Morrison VA, Picozzi V, Scott S, et al., The impact of age on
delivered dose intensity and hospitalizations for febrile
neutropenia in patients with intermediate-grade non-Hodgkin’s
lymphoma receiving initial CHOP chemotherapy: a risk factor
analysis, Clin Lymphoma, 2001;2:47–56.
34. Osby E, Hagberg H, Kvaloy S, et al., CHOP is superior to CNOP
in elderly patients with aggressive lymphoma while outcome is
unaffected by filgrastim treatment: results of a Nordic
Lymphoma Group randomized trial, Blood, 2003;101:3840–48.
35. Repetto L, Biganzoli L, Koehne CH, et al., EORTC Cancer in the
Elderly 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 with
haematological 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-line
VNCOP-B regimen experience on 350 patients, Blood, 1999;94:
33–8.
38. Crivellari D, Bonetti M, Castiglione-Gertsch M, et al., Burdens
and benefits of adjuvant cyclophosphamide, methotrexate, and
fluorouracil and tamoxifen for elderly patients with breast
cancer: 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 vivo
recombinant methionyl human granulocyte colony-stimulating
factor on the neutrophil response and peripheral blood
colony-forming cells in healthy young and elderly adult
volunteers, Blood, 1994;84:2923–9.
40. Shank WA Jr, Balducci L, Recombinant hemopoietic growth
factors: comparative hemopoietic response in younger and older
subjects, J Am Geriatr Soc, 1992;40:151–4.
41. Doorduijn JK, van der Holt B, van Imhoff GW, et al., CHOP
compared with CHOP plus granulocyte colony-stimulating factor
in 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 guidelines
for the use of granulocyte-colony stimulating factor to reduce
the incidence of chemotherapy-induced febrile neutropenia in
adult patients with lymphomas and solid tumours, Eur J Cancer,
2006;42:2433–53.
43. Lyman GH, Kleiner JM, Summary and comparison of myeloid
growth factor guidelines in patients receiving cancer
chemotherapy, J Natl Compr Canc Netw, 2007;5:217–28.
44. Smith TJ, Khatcheressian J, Lyman GH, et a., 2006 update of
recommendations for the use of white blood cell growth
factors: an evidence-based clinical practice guideline, J Clin
Oncol, 24:3187-205, 2006
45. Lyman GH, Guidelines of the National Comprehensive Cancer
Network on the use of myeloid growth factors with cancer
chemotherapy: a review of the evidence, J Natl Compr Canc
Netw, 2005;3:557–71.
46. Lyman GH, Kuderer N, Greene J, et al., The economics of febrile
neutropenia: implications for the use of colony-stimulating
factors, Eur J Cancer, 1998;34:1857–64.
47. Lyman GH, Kuderer NM, The economics of the
colony-stimulating factors in the prevention and treatment of
febrile neutropenia, Crit Rev Oncol Hematol, 2004;50:129–46.
48. Eldar-Lissai A, Cosler LE, Culakova E, et al., Economic analysis
of prophylactic pegfilgrastim in adult cancer patients receiving
chemotherapy, Value Health, 2001;11:172–9.
49. Lyman GH, Lyman CG, Sanderson RA, et al., Decision analysis
of hematopoietic growth factor use in patients receiving cancer
chemotherapy, J Natl Cancer Inst, 1993;85:488–93.
50. Cosler LE, Calhoun EA, Agboola O, et al., Effects of indirect and
additional direct costs on the risk threshold for prophylaxis with
colony-stimulating factors in patients at risk for severe
neutropenia from cancer chemotherapy, Pharmacotherapy,
2004;24:488–94.
Lyman_subbed.qxp 17/4/09 09:30 Page 16

5. European Oncology Nursing
Society (EONS)
INTRODUCTION
The European Oncology Nursing Society (EONS) has provided support
to cancer nurses across Europe since 1984.The mission of EONS is to
add value to the work of its individual members and national societies
in 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 cancer
treatments, new technologies, psychosocial care and health care provi-
sion has meant a significant shift in the way nurses apply their clinical
skills and knowledge in the workplace. However, the professional devel-
opment and status of cancer nurses across Europe is not uniform and
EONS strategic agenda (CARE) aims to address this inequality by
working with oncology nurses through their national societies.
STRATEGIC PRIORITIES
Communication
Communicating with and to oncology nurses across Europe remains
a challenge. Developing diverse communication pathways is complex
and EONS is committed to doing this by continuing to produce and
distribute (through the national societies) a newsletter four times
a year.The EONS website (part of Cancerworld) is an established
forum for cancer nurses and EONS will be developing multi-language
sections within the site as well as options for interactive forums to
promote professional discussion, information and networking.The
European Journal of Oncology Nursing continues to be one of the
leading cancer journals and celebrated 10 years of publication in 2006.
Political Agenda
EONS is one of the professional cancer societies that form part of the
umbrella organisation renamed ECCO in 2007 (European CanCer
Organisation) previously known as FECS – Federation of European Cancer
Societies.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 Nursing
Specialist and Nursing Interest Groups.The organisation acts as a platform
to represent nursing in the wider political forum.
Research
Promoting evidence based clinical practice through research has
always been a core function of EONS.Various grants are distributed
through EONS to promote and facilitate research initiatives. One
of the priorities is to develop a European cancer nursing research
network which will enable wider collaboration, participation and
sharing of research evidence as well as build a body of research and
development expertise.
Education
The themes as priorities in education are to develop cancer nurse
educators to develop and accredit teaching programmes which have
education quality standards as part of the review process. Inequality
in accessing post-registration cancer nursing education exists across
Europe.Alongside this work is the commitment to develop specialist
education and leadership programmes which can be viewed in
www.cancerworld.org/eons
Notwithstanding the busy agenda the patient experience lies at the
heart of the CARE Strategy. By utilising and working in collaboration
with patients, EONS will continue to provide a unique contribution
to the agenda of cancer care in Europe, whilst promoting the unique
contribution of cancer nursing in this processs.
For more information on EONS, please contact the secretariat at
eons.secretariat@skynet.be
CARE encompasses four
bodies of work:
C Communication
A Activities for the Political agenda
R Research
E Education
EONS_ad.qxp 17/4/09 09:32 Page 17