Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

Katy L Cooper, Jason Madan, Sophie Whyte, Matt D Stevenson, Ron L Akehurst, Katy L Cooper, Jason Madan, Sophie Whyte, Matt D Stevenson, Ron L Akehurst

Abstract

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy.

Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity.

Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98).

Conclusions: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Figures

Figure 1
Figure 1
Flow chart for identification of relevant studies.
Figure 2
Figure 2
Primary G-CSFs versus no primary G-CSF: FN incidence. Cancer types for each study are shown after the author and date. CHOP and CNOP = chemotherapy regimens for NHL (see Table 1 footnote); NHL = non-Hodgkin's lymphoma; SCLC = small-cell lung cancer; solid = solid tumours. *Indicates studies in patients aged ≥ 60 or ≥ 65 years.
Figure 3
Figure 3
Pegfilgrastim versus filgrastim: FN incidence. Cancer types for each study are shown after the author and date. HL = Hodgkin's lymphoma; NHL = non-Hodgkin's lymphoma. *Indicates studies in patients aged ≥ 60 or ≥ 65 years. In the Holmes 2002 (phase II) study,[37] FN incidence in the filgrastim arm was reported as 2/25, which was incorrectly converted to 12%. The absolute numbers (2/25) have been used in this analysis. Therefore the resulting relative risk differs slightly from that reported in the previous systematic review by Pinto (2007),[19] which used the 12% figure.

References

    1. Kuderer N, Dale D, Crawford J, Cosler L, Lyman G. Mortality, Morbidity, and Cost Associated with Febrile Neutropenia in Adult Cancer Patients. CANCER. 2006;106:2258–2266. doi: 10.1002/cncr.21847.
    1. Brown R, Hutton J, Burrell A. Cost Effectiveness of Treatment Options in Advanced Breast Cancer in the UK. Pharmacoeconomics. 2001;19:1091–1102. doi: 10.2165/00019053-200119110-00003.
    1. Brown RE, Hutton J. Cost-utility model comparing docetaxel and paclitaxel in advanced breast cancer patients. Anticancer Drugs. 1998;9:899–907. doi: 10.1097/00001813-199811000-00009.
    1. Shayne M, Crawford J, Dale D, Culakova E, Lyman G. for the ANC Study Group. Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat. 2006;100:255–262. doi: 10.1007/s10549-006-9254-4.
    1. Bonadonna G, Moliterni A, Zambetti M, Daidone M, Pilotti S, Gianni L. et al.30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ. 2005;330:217–222. doi: 10.1136/bmj.38314.622095.8F.
    1. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood. 1996;88:1907–1929.
    1. Green M, Koelbl H, Baselga J, GAlid A, Guillem V, Gascon P. et al.A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Annals of Oncology. 2003;14:29–35. doi: 10.1093/annonc/mdg019.
    1. Holmes F, O'Shaughnessy J, Vukelja S, Jones S, Shogan J, Savin M. et al.Blinded, Randomized, Multicenter Study to Evaluate Single Administration Pegfilgrastim Once per Cycle Versus Daily Filgrastim as an Adjunct to Chemotherapy in Patients With High-Risk Stage II or Stage III/IV Breast Cancer. JOURNAL OF CLINICAL ONCOLOGY. 2002;20:727–731. doi: 10.1200/JCO.20.3.727.
    1. Chevallier B, Chollet P, Merrouche Y, Roche H, Fumoleau P, Kerbrat P. et al.Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer. J Clin Oncol. 1995;13:1564–1571.
    1. Bui BN, Chevallier B, Chevreau C, Krakowski I, Peny AM, Thyss A. et al.Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity. J Clin Oncol. 1995;13:2629–2636.
    1. Molineux G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta) Curr Pharm Des. 2004;10:1235–1244. doi: 10.2174/1381612043452613.
    1. Molineux G. Pegfilgrastim: using pegylation technology to improve neutropenia support in cancer patients. Anticancer Drugs. 2003;14:259–264. doi: 10.1097/00001813-200304000-00002.
    1. Aapro MS, Bohlius J, Cameron DA, Dal LL, Donnelly JP, Kearney N. et al.2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8–32.
    1. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L. et al.2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–3205. doi: 10.1200/JCO.2006.06.4451.
    1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Myeloid Growth Factors. 2011. 1-5-2010.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269.
    1. PRISMA statement website. 2009.
    1. Kuderer N, Dale D, Crawford J, Lyman G. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. JOURNAL OF CLINICAL ONCOLOGY. 2007;25:3158–6731. doi: 10.1200/JCO.2006.08.8823.
    1. Pinto L, Liu Z, Doan Q. 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;23:2283–2295. doi: 10.1185/030079907X219599.
    1. Higgins JPT, Green S. The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions. 2009.
    1. Vogel C, Wojtukiewicz M, Carroll R, Tjulandin S, Barajas-Figueroa L, Wiens B. et al.First and Subsequent Cycle Use of Pegfilgrastim Prevents Febrile Neutropenia in Patients With Breast Cancer: A Multicenter, Double-Blind, Placebo-Controlled Phase III Study. J Clin Oncol. 2005;23:1178–1184. doi: 10.1200/JCO.2005.09.102.
    1. Balducci L, Al-Halawani H, Charu V, Tam J, Shahin S, Dreiling L. et al.Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim. Oncologist. 2007;12:1416–1424. doi: 10.1634/theoncologist.12-12-1416.
    1. Romieu G, Clemens M, Mahlberg R. Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: A randomized phase 2 trial. Critical Reviews in Oncology/Hematology. 2007;64:64–72. doi: 10.1016/j.critrevonc.2006.12.007.
    1. Hecht JR, Pillai M, Gollard R, Dreiling L, Mo M, Malik I. Pegfilgrastim in colorectal cancer (CRC) patients (pts) receiving every-two-week (Q2W) chemotherapy (CT): Long-term results from a phase II, randomized, controlled study. JOURNAL OF CLINICAL ONCOLOGY. 2009;27:Abstract 4072.
    1. Doorduijn JK, van der HB, van Imhoff GW, van der Hem KG, Kramer MH, van Oers MH. et al.CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2003;21:3041–3050. doi: 10.1200/JCO.2003.01.076.
    1. Osby E, Hagberg H, Kvaloy S, Teerenhovi L, Anderson H, Cavallin-Stahl E. 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;101:3840–3848. doi: 10.1182/blood-2002-10-3238.
    1. Zinzani PL, Pavone E, Storti S, Moretti L, Fattori PP, Guardigni L. et al.Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. Blood. 1997;89:3974–3979.
    1. Pettengell R, Gurney H, Radford J, Deakin D. Granulocyte Colony-Stimulating Factor to Prevent Dose-Limiting Neutropenia in Non-Hodgkin's Lymphoma: A Randomized Controlled Trial. Blood. 1992;80:1430–1436.
    1. Timmer-Bonte J, de Boo T, Smit H, Biesma B, Wilschut F, Cheragwandi S. et al.Prevention of Chemotherapy-Induced Febrile Neutropenia by Prophylactic Antibiotics Plus or Minus Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer: A Dutch Randomized Phase III Study. J Clin Oncol. 2005;23:7974–7984. doi: 10.1200/JCO.2004.00.7955.
    1. Trillet-Lenoir V, Green J, Manegold C, Von Pawel J, Gatzemeier U, Lebeau B. et al.Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. European Journal of Cancer. 1993;29:319–324. doi: 10.1016/0959-8049(93)90376-Q.
    1. Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I. 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. 1991;325:164–170. doi: 10.1056/NEJM199107183250305.
    1. Fossa SD, Kaye SB, Mead GM, Cullen M, de WR, Bodrogi I. et al.Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. J Clin Oncol. 1998;16:716–724.
    1. del Giglio A, Eniu A, Ganea-Motan D, Topuzov E, Lubenau H. XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer. 2008;8:332. doi: 10.1186/1471-2407-8-332.
    1. Gisselbrecht C, Haioun C, Lepage E, Bastion Y, Tilly H, Bosly A. et al.Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte. Leuk Lymphoma. 1997;25:289–300.
    1. Gebbia V, Valenza R, Testa A, Cannata G, Borsellino N, Gebbia N. A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy. Anticancer Res. 1994;14:731–734.
    1. Gebbia V, Testa A, Valenza R, Borsellino N, Cipolla C, Cannata G. et al.A prospective evaluation of the activity of human granulocyte-colony stimulating factor on the prevention of chemotherapy-related neutropenia in patients with advanced carcinoma. J Chemother. 1993;5:186–190.
    1. Holmes F, Jones S, O'Shaughnessy J, Vukelja S, George T, Savin M. et al.Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Annals of Oncology. 2002;13:903–909. doi: 10.1093/annonc/mdf130.
    1. Grigg A, Solal-Celigny P, Hoskin P, Taylor K, McMillan A, Forstpointner R. et al.Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma. Leuk Lymphoma. 2003;44:1503–1508. doi: 10.1080/1042819031000103953.
    1. Vose J, Crump M, Lazarus H, Emmanouilides C, Schenkein D, Moore J. et al.Randomized, Multicenter, Open-Label Study of Pegfilgrastim Compared With Daily Filgrastim After Chemotherapy for Lymphoma. JOURNAL OF CLINICAL ONCOLOGY. 2003;21:514–519. doi: 10.1200/JCO.2003.03.040.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅