Schwartzberg_edit.qxp 31/10/08 12:16 Page 26
Supportive Oncology
Management of Chemotherapy-induced Neutropoenia
a report by
Lee S Schwartzberg
Medical Director, The West Clinic, and Clinical Professor of Medicine, University of Tennessee College of Medicine
During the past several years, a number of novel targeted anticancer drugs Subsequent evaluation of the MASCC index has validated the prognostic
have been integrated into clinical practice. Despite the efficacy and variety accuracy of the score in other patient populations.
5
The tool has proven
of new agents, traditional myelosuppressive chemotherapy remains the clinical utility in allowing patients at low risk to be treated successfully with
backbone of cancer treatment. In addition, the new biologicals often oral antibiotics and be followed as outpatients.
6,7
Attempts to incorporate
increase myelotoxicity when added to standard chemotherapy regimens. blood inflammatory marker analysis into the clinical scale did not add to
Therefore, myelosuppression remains the most common toxicity the predictive value of the MASCC score.
8
A risk-adapted strategy utilising
encountered in the oncology clinic today and this complication is likely to the MASCC index allows a significant fraction of low-risk patients to be
remain a serious problem indefinitely. Chemotherapy-induced neutropoenia treated in the outpatient setting when follow-up is careful and adherence
(CIN) is defined clinically as an absolute neutrophil count (ANC) of to medical care is high.
9
Nonetheless, the majority of patients with FN do
<1.0x10
9
/l, at which point the risk of infection begins to rise. This risk is require at least some inpatient observation and treatment with
related both to the depth and duration of neutropoenia.
1
An ANC below intravenous antibiotics. The costs associated with FN and its treatment are
0.5x10
9
/l is therefore considered severe neutropoenia (SN) and febrile substantial and are not limited to the direct cost of hospitalisations. It is likely
neutropoenia (FN) is defined as a temperature >38.2ºC on two that even separating out low-risk patients for outpatient treatment will not
determinations with an ANC <0.5x10
9
/l, which indicates a high likelihood of have a great impact on costs, which are driven mostly by the fraction of
a localised or systemic infection. FN requires prompt intervention with broad patients who have severe complications.
10
Health systems may therefore be
spectrum antibiotics until endogenous recovery of the bone marrow occurs. obligated to expend increased resources caring for patients with FN.
During FN, patients are at risk of overwhelming infection in the absence of
neutrophils and anti-infectives. Risk of SN and FN from chemotherapy depends on several factors, most
importantly the myelosuppressive intensity of the chemotherapy regimen
Despite the availability of broad-spectrum antibiotics, FN continues to have utilised. One way to reduce the risk of CIN is to reduce the drug dosage
significant consequences including increased morbidity, hospitalisation, delivered. However, substantial direct and retrospective evidence suggests
mortality and excessive cost. Even in recent years, mortality from FN has that reduction in relative dose intensity is deleterious in terms of disease-free
remained high when patients have co-morbidities. Reviews of hospitalised outcome and overall survival in the curative and perhaps life-prolonging
patients have clearly documented risk factors for complications of FN.
2,3
CIN indications for chemotherapy.
11,12
CIN is a common cause of chemotherapy
and FN occur across a wide spectrum of patients who harbour dose delay and dose reduction,
13
and prolonged recovery from FN may
heterogeneous disease and co-morbid conditions. Clearly, some patients are compromise subsequent cycle delivery of full dose on schedule.
at low risk of developing serious complications from FN and perhaps can be
spared intensive therapy. The Multinational Association for Supportive Care Colony-stimulating Factors for
in Cancer (MASCC) risk index was developed in 2000 to be a validated, Chemotherapy-induced Neutropoenia
clinically useful tool to help sort patients into low- and high-risk groups.
4
Risk An alternative to reducing dose is supportive care utilising granulocyte
factors including symptom burden, chronic obstructive pulmonary disease colony-stimulating factor (G-CSF) to stimulate the proliferation,
(COPD), hypotension, solid tumoir histology, outpatient status, dehydration differentiation, survival and functionability of myeloid cells, resulting in an
and age <60 years were defined as significant in a derivation set of several increase in circulating neutrophils. Recombinant G-CSF has been available
hundred patients. The MASCC score can distinguish patients at low versus since the early 1990s and has transformed the approach to CIN.
high risk with a high positive predictive value. Recombinant human G-CSF is marketed as filgrastim (Neupogen), an
Escherichia coli-derived non-glycosylated protein, and lenograstim
(Granocyte), a glycosylated version derived from Chinese hamster ovary
Lee S Schwartzberg is a Clinical Professor of Medicine at the
University of Tennessee College of Medicine and a Senior
cells. Regulatory approval of filgrastim occurred after a US multicentre
Partner and Medical Director at the West Clinic, a 30-
double-blind placebo-controlled study demonstrated a reduction in FN from
physician private oncology and haematology practice in
77 to 40% in small-cell lung cancer patients receiving G-CSF after intensive
Memphis. He is Founder and Medical Director of the Baptist
Centers for Cancer Care Cancer Genetics Program and also
myelosuppressive chemotherapy.
14
In addition, the incidence and duration
serves as Chair of the Baptist Comprehensive Breast Center
of SN, days in hospital and days of antibiotics, and documented infection
multidisciplinary programme. Professor Schwartzberg’s
major research interests are new therapeutic approaches to
were also reduced significantly. These results were confirmed in a European
breast cancer, targeted therapy and supportive care. He is the founding Editor in Chief of study with a similar proportional benefit.
10
Multiple other trials in a variety
Community Oncology and serves on the Editorial Board of the Journal of Supportive Oncology.
of disease settings and with base FN rates of 30–50% without growth factor
E: lscwartzberg@westclinic.com support show similar reduction in FN rates and other markers of CIN when
filgrastim was utilised after myelosuppressive chemotherapy.
16–18
26 © TOUCH BRIEFINGS 2008
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99