• Peter C Gøtzsche and Helle Krogh Johansen.
• The Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, 7811, Copenhagen, Denmark, DK-2100.
• Cochrane Db Syst Rev. 2014 Sep 4; 2014 (9): CD000026CD000026.

BackgroundSystemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.ObjectivesTo assess whether commonly used antifungal drugs decrease mortality in cancer patients with neutropenia.Search MethodsWe searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.Selection CriteriaRandomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole or voriconazole compared with placebo or no treatment in cancer patients with neutropenia.Data Collection And AnalysisThe two review authors independently assessed trial eligibility and risk of bias, and abstracted data.Main ResultsThirty-two trials involving 4287 patients were included. Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0.73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial to allow a meaningful overview. For the 2011 and 2014 updates no additional trials were identified for inclusion.Authors' ConclusionsIntravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is introduced in cancer patients with neutropenia.

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