Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy- A randomized, controlled trial

Background: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting, Objective: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. Design: An open randomized, controlled, multicenter trial, powered for equi valence. Setting: 60 oncology centers in 10 countries. Patients: 384 neutropenic patients with cancer who had persistent fever tha t did not respond to antibiotic therapy. Intervention: Intravenous amphoter icin B or intravenous itraconazole followed by oral itraconazole solution. Measurements: Defervescence, breakthrough fungal infection, drug-related ad verse events, and death. Results: For itraconazole and amphotericin B, the median duration of therap y was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 pa tients showed response rates of 47% and 38% for itraconazole and amphoteric in B, respectively (difference, 9.0 percentage points [95% Cl, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itr aconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lo wer with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphoter icin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infec tions (S patients in each group) and mortality rates (19 deaths in the itra conazole group and 25 deaths in the amphotericin B group) were similar. Six ty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days. Conclusions: Itraconazole and amphotericin B have at least equivalent effic acy as empirical antifungal therapy in neutropenic patients with cancer. Ho wever, itraconazole Is associated with significantly less toxicity.