Prevention of fungal infections in patients with cancer with antifungal drugs

Gøtzsche PC, Johansen HK

Published Online:

November 9, 2011

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

Abstract (click to read)

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 the effect of antifungal drugs in cancer patients with neutropenia.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2007, PubMed (November 2007) and the reference lists of articles. We searched the proceedings of the ICAAC (from 1990 to 2007), General Meeting of the ASM (from 1990 to 2007), and the European Congress of Clinical Microbiology and Infectious Diseases (1995 to 2007) and contacted researchers in the field. For the 2011 update we searched PubMed from 1966 to 18 July 2011 and the reference lists of 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, risk of bias and abstracted data.

Main results:

Thirty-two trials involving 4287 patients were included. Prophylactic or empirical treatment with amphotericin B decreased total mortality significantly (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimates 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 update 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 in cancer patients with neutropenia is instituted.

This record should be cited as:

Gøtzsche PC, Johansen HK. Routine versus selective antifungal administration for control of fungal infections in patients with cancer. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD000026. DOI: 10.1002/14651858.CD000026

Assessed as up to date:

July 18, 2011

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Generic cancer care > Infections in neutropenic patients

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Prevention of fungal infections in patients with cancer with antifungal drugs

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