Abstract

Background

Systemic 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.

Objectives

To assess whether commonly used antifungal drugs decrease mortality in cancer patients with neutropenia.

Search methods

We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.

Selection criteria

Randomised 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 analysis

The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.

Main results

Thirty‐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' conclusions

Intravenous 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.

Author(s)

Peter C Gøtzsche, Helle Krogh Johansen

Abstract

Plain language summary

Prevention of fungal infections in patients with cancer with antifungal drugs

Cancer patients receiving chemotherapy or a bone marrow transplant are at risk of fungal infections. These can be life‐threatening, especially when they spread throughout the body. Those patients with low white cell counts (neutropenia) are particularly at risk. Antifungal drugs are often given as a routine preventive measure, or when people who are at risk have a fever. The review found that intravenous amphotericin B could reduce the number of deaths. Three of the drugs, amphotericin B, fluconazole and itraconazole, reduced fungal infections.

Author(s)

Peter C Gøtzsche, Helle Krogh Johansen

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Intravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is instituted in cancer patients with neutropenia.

Implications for research 

It may be difficult to justify further placebo‐controlled trials whereas there is a need for unbiased trials comparing intravenous amphotericin B with other antifungal drugs. Such trials should comprise at least 1000 patients and they should include data on length of hospital stay and similar measures, allowing cost‐benefit analyses to be performed. Data on the incidence of bacterial infections should be collected since azole compounds might increase the risk of such infections.

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