Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia.
OBJECTIVE
To determine whether antifungal agents given prophylactically or empirically decrease morbidity and mortality in patients with cancer complicated by neutropenia.


METHODS
Meta-analysis of randomised trials of amphotericin B, various lipid soluble formulations of amphotericin B (for example, AmBisome), fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment.


METHODS
Trials conducted anywhere in the world.


METHODS
Patients with cancer complicated by neutropenia.


METHODS
Mortality, invasive fungal infection (defined as positive blood culture, oesophageal candidiasis, or lung or deep tissue infection), and colonisation.


RESULTS
24 trials with 2758 randomised patients were reviewed; the total number of deaths was 434. Prophylactic or empirical treatment with antifungals as a group bad no effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14). Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the studies were small and the difference in number of deaths was only 15. Antifungal treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to 0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated (95% confidence interval to 48 to 158) one case of fungal invasion was prevented in surviving patients.


CONCLUSIONS
There seems to be no survival benefit of antifungal agents given prophylactically or empirically to patients with cancer complicated by neutropenia. These agents should be restricted to patients with proved infection and those in randomised trials. A large, definitive placebo controlled trial of amphotericin B is needed.
Gøtzsche
P C
PC
Nordic Cochrane Center, Rigshospitalet, Copenhagen, Denmark.
Johansen
H K
HK
D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use*; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D007654:Ketoconazole / Q000627:therapeutic use; D008825:Miconazole / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic
D000935:Antifungal Agents; D017964:Itraconazole; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole