title: Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia.
abstract: 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.
authors.affiliation: Nordic Cochrane Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: P C
authors.initials: PC
authors.lastname: Gøtzsche
authors.forename: H K
authors.initials: HK
authors.lastname: Johansen
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole