Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (I.V. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with IV ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of IV ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS Despite its theoretic advantages, the authors found no evidence that IV ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole. Cancer 2004. © 2003 American Cancer Society.