A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer

PURPOSE: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cance r. PATIENTS AND METHODS: A total of 317 neutropenic patients (<500 cells/mm(3) ) with persistent or recrudescent fever despite 4 or more days of antibacte rial therapy were randomly assigned to receive either fluconazole (400 mg i ntravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criter ia, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patie nt was afebrile, had no clinical or microbiological evidence of fungal infe ction, and did not require study termination due to lack of efficacy, drug toxicity, or death. RESULTS: A satisfactory response occurred in 68% of the patients treated wi th fluconazole (107 of 158 patients) and in 67% of patients treated with am photericin B (106 of 159 patients). Progressive or new fungal infections du ring therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphoteri cin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse eve nts related to study drug (especially fryer, chills, renal insufficiency, e lectrolyte disturbances, and respiratory distress) occurred more often in p atients treated with amphotericin B (128 [81%] of 159 patients) than patien ts treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven ( 7%) patients treated with amphotericin B but only 1 (1%) patient treated wi th fluconazole were terminated from the study owing to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole ver sus 34 [21%] patients treated with amphotericin B) and mortality from funga l infection (7 [4%] patients treated with fluconazole versus 5 [3%] patient s treated with amphotericin B) were similar in each study group. CONCLUSIONS: Intravenous fluconazole can be an effective and safe: alternat ive to amphotericin B for empiric antifungal therapy in many febrile neutro penic patients. However, because fluconazole may he ineffective in the trea tment of Aspergillus, patients at risk for that infection should be evaluat ed by chest radiograph, computed tomographic scanning, and cultures before the use of empiric fluconazole therapy. Am I Med. 2000; 108:282-289. (C) 20 00 by Excerpta Medics, Inc.