Kuderer Nicole M, Dale David C, Crawford Jeffrey, Lyman Gary H
University of Rochester School of Medicine and Dentistry, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
J Clin Oncol. 2007 Jul 20;25(21):3158-67. doi: 10.1200/JCO.2006.08.8823.
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).
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.
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.
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.
预防性粒细胞集落刺激因子（G-CSF）的随机对照试验（RCT）已证明全身化疗后发热性中性粒细胞减少症（FN）显著降低。最近发表了几项RCT，研究G-CSF对死亡率和相对剂量强度（RDI）的影响。
对所有已报道的将成人实体瘤和恶性淋巴瘤患者中主要预防性使用G-CSF与安慰剂或未治疗对照进行比较的RCT进行全面的系统评价和荟萃分析，不受语言限制，使用电子数据库、会议论文集和手工检索技术。两名评价者独立提取数据。基于Mantel-Haenszel法以及DerSimonian和Laird法估计相对危险度（RR）及95%可信区间（CI）的汇总估计值。
共纳入17项RCT，包括3493例患者。与对照组相比，G-CSF使感染相关死亡率的RR降低45%（RR = 0.55；95%CI，0.33至0.90；P = 0.018）；早期死亡率（化疗期间全因死亡率）降低40%（RR = 0.60；95%CI，0.43至0.83；P = 0.002）；FN降低46%（RR = 0.54；95%CI，0.43至0.67；P < 0.001）。与对照患者相比，接受G-CSF的患者平均RDI显著更高（P < 0.001）。对照组中有10.4%的患者以及G-CSF组中有19.6%的患者报告有骨或肌肉骨骼疼痛（RR = 4.03；95%CI，2.15至7.52；P < 0.001）。在允许对对照组进行二级G-CSF预防的研究以及两个治疗组均同时使用预防性抗生素的三项试验中，观察到G-CSF可显著降低FN。
预防性使用G-CSF可降低FN和早期死亡的风险，包括感染相关死亡率，同时增加RDI和肌肉骨骼疼痛。评估G-CSF对无病生存期和总生存期影响的数据不足。
