Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: Benefit based on purpose and intensity of cytotoxic therapy

A randomized, double-blind trial comparing oral fluconazole (400 mg daily) with placebo as prophylaxis for adult patients receiving intensive cytotoxi c therapy for acute leukemia or autologous bone marrow transplantation was conducted in 14 Canadian university-affiliate hospitals. Although fluconazo le prophylaxis did not obviate the need for parenteral antifungal therapy c ompared with placebo (81 [57%] of 141 vs. 67 [50%] of 133, respectively), i ts use resulted in fewer superficial fungal infections (10 [7%] of 141 vs, 23 [18%] of 131, respectively; P = .02) and fewer definite and probable inv asive fungal infections (9 vs. 32, respectively; P = .0001), Fluconazole re cipients had fewer deaths attributable to definite invasive fungal infectio n (1 of 15 vs. 6 of 15, respectively; P = .04) and achieved more frequent s uccess without fungal colonization (52 [37%] of 141 vs. 27 [20%] of 133, re spectively; P = .004; relative risk reduction, 85%) than did placebo recipi ents. Patients benefiting the most from fluconazole prophylaxis included th ose with acute myeloid leukemia who were undergoing induction therapy with cytarabine plus anthracycline-based regimens and those receiving marrow aut ografts not supported with hematopoietic growth factors. Fluconazole prophy laxis reduces the incidence of superficial fungal infection and invasive fu ngal infection and fungal infection-related mortality among patients who ar e receiving intensive cytotoxic chemotherapy for remission induction.