Originally published as JCO Early Release 10.1200/JCO.2007.12.3851 on October 1 2007

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Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis

Eyal Robenshtok, Anat Gafter-Gvili, Elad Goldberg, Miriam Weinberger, Moshe Yeshurun, Leonard Leibovici, Mical Paul

From the Department of Medicine E, Hematology Department, and Infectious Disease Unit, Rabin Medical Center, Beilinson Campus, Petah-Tiqva; Sackler School of Medicine, Tel Aviv University, Ramat Aviv; and Infectious Disease Unit, Assaf Harofeh Medical Center, Zerifin, Israel

Address reprint requests to Eyal Robenshtok, MD, Department of Medicine E, Rabin Medical Center, Beilinson Campus, 49100 Petah-Tiqva, Israel; e-mail: Eyalr2{at}clalit.org.il

Purpose: 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.

Conclusion: 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.

published online ahead of print at www.jco.org on October 1, 2007

Supported in part by the Young Investigator Research Grant of the Rabin Medical Center.

Presented in part in poster format at the 17th European Congress of Clinical Microbiology and Infectious Diseases, Munich, Germany, March 31 to April 3, 2007.

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