Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Robenshtok
Eyal
E
Department of Medicine E, Rabin Medical Center, Petah-Tiqva, Israel. Eyalr2@clalit.org.il
Gafter-Gvili
Anat
A
Goldberg
Elad
E
Weinberger
Miriam
M
Yeshurun
Moshe
M
Leibovici
Leonard
L
Paul
Mical
M
D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D002648:Child; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy / Q000382:microbiology* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000935:Antifungal Agents