Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: A systematic review

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.