FAILURE OF FLUCONAZOLE PROPHYLAXIS TO REDUCE MORTALITY OR THE REQUIREMENT OF SYSTEMIC AMPHOTERICIN-B THERAPY DURING TREATMENT FOR REFRACTORY ACUTE MYELOID-LEUKEMIA - RESULTS OF A PROSPECTIVE RANDOMIZED PHASE-III STUDY

BACKGROUND. Invasive fungal infections have increasingly become a matt er of concern with regard to patients receiving intensive myelosuppres sive therapy for hematologic malignancies. Such infections, especially prolonged neutropenia systemic fungal infections, may contribute subs tantially to infectious complications and early death. Measures for ea rly detection and effective prophylactic strategies using active and n ontoxic antifungal agents are therefore urgently needed. METHODS. The current randomized study was initiated to assess the efficacy of oral fluconazole as systemic antifungal prophylaxis for high risk patients with recurrent acute myeloid leukemia undergoing intensive salvage the rapy. RESULTS. Of 68 fully evaluable patients, 36 were randomized to f luconazole in addition to standard prophylaxis with oral co-trimoxazol , colistin sulphate, and amphotericin B suspension, and 32 were random ized to standard prophylaxis only. No major differences between the tw o groups were observed in the number of episodes of fever of unknown o rigin (61% vs. 50%) or clinically defined infections (56% vs. 50%). Mi crobiologically defined infections were more frequent in the fluconazo le group (50% vs. 31%), mainly due to a higher incidence of bacteremia s (42% vs. 22%). There were two cases of proven invasive fungal infect ions in each group. Systemic amphotericin B was administered more freq uently to patients receiving fluconazole prophylaxis (56% vs. 28%). Fl uconazole prophylaxis had no impact on the rate of early death or over all survival. CONCLUSIONS. For patients with high risk recurrent acute myeloid leukemia undergoing intensive salvage therapy, antifungal pro phylaxis with fluconazole was not superior to standard prophylaxis onl y. (C) 1998 American Cancer Society.