Safety and Efficacy of Itraconazole Compared to Amphotericin B as Empirical Antifungal Therapy for Neutropenic Fever in Patients with Haematological Malignancy*

Abstract

Safety, tolerability and efficacy of itraconazole and amphotericinB (AMB) were compared for empirical antifungal treatmentof febrile neutropenic cancer patients. Patients and Methods:In an open, randomised study, 162 patients with at least 72 h ofantimicrobial treatment received either intravenous followed byoral itraconazole suspension or intravenous AMB for a maximum of28 days. Permanent discontinuation of study medication due to anyadverse event was the primary safety parameter. Efficacy parametersincluded response and success rate for both treatment groups.Results: Significantly fewer itraconazole patients discontinued treatmentdue to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001).The main reason for discontinuation was a rise in serum creatinine(1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantlyhigher and more drug-related adverse events occurred in the AMBgroup. Intention-to-treat (ITT) analysis showed favourable efficacyfor itraconazole: response and success rate were both significantlyhigher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, bothp < 0.0001). Treatment failure was markedly reduced in itraconazolepatients (25.9 vs. 43.2%), largely due to the better tolerability.Conclusions: Itraconazole was tolerated significantly better thanconventional AMB and also showed advantages regarding efficacy.This study confirms the role of itraconazole as a useful andsafe agent in empirical antifungal therapy of febrile neutropeniccancer patients.