A systematic review including 64 RCTs with a total of 13 015 subjects was abstracted in DARE. A systematic review including 64 RCTs with 13 015 participants was abstracted in DARE. Afebrile cancer patients after chemotherapy or haematopoietic stem-cell transplantation (HSCT) were included. The majority of patients were hospitalized adults with acute leukaemia. Treatment doses and durations and follow-up periods varied between studies. Systemic antifungal agents included fluconazole, itraconazole, ketoconazole, voriconazole and liposomal amphotericin. The primary outcome was all-cause mortality. Secondary outcomes included invasive fungal infections (IFI) and fungal-related death.
• Systemic antifungals significantly reduced all-cause mortality compared to placebo/no treatment/non-systemic antifungals (RR 0.84 at the end of follow-up, 95% CI 0.74 to 0.95, 31 studies; RR 0.79 for 30-day mortality, 95% CI 0.68 to 0.92). Fungal-related mortality was also reduced with systemic antifungals (RR 0.55, 95% CI 0.41 to 0.74, 33 studies).
• Significant increase in adverse events were reported with itraconazole compared to fluconazole, resulting in the study being discontinued (RR 2.50, 95% CI 1.89 to, 3.33; 7 studies). No other significant differences were reported in comparisons of two systemic antifungal agents (19 studies in all).
• Significant reductions in IFI were reported with fluconazole versus amphotericin B (RR 0.49, 95% CI 0.28 to 0.86; 3 studies). More adverse events were reported with amphotericin B (RR 6.67, 95% CI 2.6 to 16.7).
• Posaconazole compared with fluconazole or itraconazole (2 studies) produced a borderline significant reduction in all-cause mortality (RR 0.77, 95% CI 0.59 to 1.01), and a significant reduction in fungal-related mortality (RR 0.25, 95% CI 0.11 to 0,57), documented or probable IFIs (RR 0.47, 95% CI 0.3 to 0.74) and documented invasive Aspergillus infections (RR 0.22, 95% CI 0.11 to 0.42).
Comment: The quality of evidence is downgraded by imprecise results (wide confidence intervals).