Amphotericin B vs fluconazole for controlling fungal infections in neutropenic cancer patients.
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.


OBJECTIVE
To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.


METHODS
MEDLINE and Cochrane Library (March 2000). Letters, abstracts, and unpublished trials. The industry and authors were contacted.


METHODS
Randomised trials comparing fluconazole with amphotericin B.


METHODS
Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by both authors independently.


RESULTS
Thirteen trials (2977 patients) were included. In 3 large 3-armed trials, which comprised 43% of the patients, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is an ineffective drug in theses circumstances, this approach creates a bias in favour of fluconazole. Furthermore, 79% of the patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. It was unclear whether there was overlap among the "polyene" trials. We were unable to obtain any information to clarify these issues from the trial authors or the manufacturer of fluconazole. There was no significant difference in effect between fluconazole and amphotericin B. Apart from the "polyene" trials, more patients dropped out of the study when they received amphotericin B.


CONCLUSIONS
Amphotericin B had been disfavoured in most of the trials through their design or analysis. Since intravenous amphotericin B is the only antifungal agent with a documented effect on mortality and is considerably cheaper than fluconazole, it should be preferred.
Johansen
H K
HK
The Nordic Cochrane Centre, Rigshospitalet, Dept. 7112, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. hkj@cochrane.dk
Gotzsche
P C
PC
D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D016001:Confidence Intervals; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000150:complications*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole