Robenshtok Eyal, Gafter-Gvili Anat, Goldberg Elad, Weinberger Miriam, Yeshurun Moshe, Leibovici Leonard, Paul Mical
Department of Medicine E, Rabin Medical Center, Petah-Tiqva, Israel.
J Clin Oncol. 2007 Dec 1;25(34):5471-89. doi: 10.1200/JCO.2007.12.3851. Epub 2007 Oct 1.
To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions.
We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data.
Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole.
Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.
评估抗真菌预防治疗对全因死亡率（作为主要结局）、侵袭性真菌感染（IFI）及不良事件的影响。许多研究评估了抗真菌预防治疗在癌症患者中的作用，但结论并不一致。
我们对随机对照试验进行了系统评价和荟萃分析，比较全身用抗真菌药与安慰剂、不干预措施或其他抗真菌药用于癌症患者化疗后预防治疗的效果。检索了Cochrane图书馆、MEDLINE、会议论文集及参考文献。两名评价者独立评估试验质量并提取数据。
64项试验符合纳入标准。与安慰剂、不治疗或非全身用抗真菌药相比，抗真菌预防治疗在随访结束时显著降低了全因死亡率（相对危险度[RR]，0.84；95%置信区间[CI]，0.74至0.95）。在异基因造血干细胞移植（HSCT）受者中，预防治疗降低了全因死亡率（RR，0.62；95%CI，0.45至0.85）、真菌相关死亡率及确诊的IFI。在急性白血病患者中，真菌相关死亡率及确诊的IFI显著降低，而死亡率差异仅为临界显著（RR，0.88；95%CI，0.74至1.06）。与氟康唑相比，伊曲康唑混悬液预防治疗降低了确诊的IFI，但生存率无差异，且代价是更多的不良事件。基于两项研究，与氟康唑相比，泊沙康唑预防治疗降低了全因死亡率（RR，0.74；95%CI，0.56至0.98）、真菌相关死亡率及IFI。
抗真菌预防治疗显著降低了化疗后患者的全因死亡率。应给予接受异基因HSCT的患者抗真菌预防治疗，高危急性白血病患者可能也应给予。
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