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Impact of Primary Prophylaxis With Granulocyte Colony-Stimulating Factor on Febrile Neutropenia and Mortality in Adult Cancer Patients Receiving Chemotherapy: A Systematic Review

Nicole M. Kuderer, David C. Dale, Jeffrey Crawford, Gary H. Lyman

From the University of Rochester School of Medicine and Dentistry, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY; University of Washington School of Medicine, Seattle, WA; and the Duke University Medical Center, Durham, NC

Address reprint requests to Nicole M. Kuderer, MD, James P. Wilmot Cancer Center, University of Rochester Medical Center, 601 Elmwood Ave, Box 704, Rochester, NY 14642; e-mail: Nicole_Kuderer{at}urmc.rochester.edu

Purpose: Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI).

Methods: A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird.

Results: Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms.

Conclusion: Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.

Supported in part by Grant No. T32HL07152-30 from the National Institutes of Health and by the Awareness of Neutropenia in Chemotherapy Study Group, which receives research support from Amgen Inc. The funding agencies were not involved in study design, analysis, writing, or finalization of this report.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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