Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients
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 compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.
Search methods
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 comparing fluconazole with amphotericin B.
Data collection and analysis
The two review authors independently assessed trial eligibility, risk of bias and abstracted data.
Main results
Seventeen trials (3798 patients, 381 deaths) were included. In two large three‐armed trials, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the "polyene" trials but were unable to obtain any information to clarify these issues further from the trial authors or from Pfizer, the manufacturer of fluconazole. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded, decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion‐related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion‐related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 update no additional trials were identified for inclusion.
Authors' conclusions
Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.
PICOs
Plain language summary
Prevention of fungal infections in cancer patients with amphotericin B or fluconazole.
Cancer patients treated with chemotherapy or who receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life‐threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever. The review could not detect a difference in effect between amphotericin B and fluconazole, but several of the trials were designed or analysed in a way that disfavoured amphotericin B which is the only antifungal drug for which an effect on mortality has been shown.
