Routine versus selective antifungal administration for control of fungal infections in patients with cancer

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 to patients with persistent fever.

OBJECTIVES: The objective of this review was to assess the effect of antifungal drugs in cancer patients with neutropenia.

SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register and MEDLINE (November 1999) and the reference lists of articles. We searched the proceedings of the ICAAC, General Meeting of the ASM (from 1990 to 1999), and the 7th European Congress of Clinical Microbiology and Infectious Diseases (1995 to 1999) and contacted researchers in the field.

SELECTION CRITERIA: Randomised trials of amphotericin B, AmBisome, fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment in cancer patients with neutropenia.

DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data.

MAIN RESULTS: Twenty-nine trials involving 3875 patients were included. Intravenous amphotericin B reduced total mortality (relative risk 0.72, 95% confidence interval 0.51 to 1.02, P=0.06) based on 8 trials. This borderline result was confirmed by three trials which compared lipid soluble amphotericin B (AmBisome) with smaller doses of standard amphotericin B; the trials demonstrated an effect of AmBisome on mortality, relative risk 0.70 (95% CI 0.50 to 0.99). The risk difference for the two estimates combined is 0.040 (95% CI 0.012 to 0.068) which means that 25 patients (95% CI 15 to 83) would need to be treated with intravenous amphotericin B to avoid one death. In contrast, fluconazole, ketoconazole, miconazole and itraconazole had no effect on mortality. The incidence of invasive fungal infection decreased with administration of amphotericin B (relative risk 0.39, 95% CI 0.20 to 0.76), fluconazole (relative risk 0.39, 95% CI 0.27 to 0.57) and itraconazole (relative risk 0.45, 95% CI 0.20 to 0.99), but not with miconazole or ketoconazole.

REVIEWER'S CONCLUSIONS: Intravenous amphotericin B is the only antifungal agent which has a documented effect on mortality, and there is not sufficient evidence to judge the relative merits of other antifungal agents. This drug should therefore be preferred for prophylactic or empirical antifungal therapy in cancer patients with neutropenia.