Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study.

Seong Hyun Jeong,Sung-Hyun Kim,Yeung-Chul Mun,Jin Seok Kim,Chul Won Choi,Joon Seong Park,Dae Young Kim,Jun Ho Jang

doi:10.1007/s00277-015-2545-2

Abstract

Micafungin, a clinically important echinocandin antifungal drug, needs to be investigated as empirical therapy in febrile neutropenia in comparison with azole compounds. A prospective randomized study was conducted to compare clinical outcomes between micafungin and intravenous itraconazole as an empirical therapy for febrile neutropenia in hematological malignancies. The antifungal drug (micafungin 100 mg or itraconazole 200 mg IV once daily) was given for high fever that was sustained despite the administration of appropriate antibiotics. Treatment success was determined by composite end points based on breakthrough invasive fungal infection (IFI), survival, premature discontinuation, defervescence, and treatment of baseline fungal infection. Duration of fever, hospital stay, and overall survival (OS) were studied. A total of 153 patients were randomized to receive micafungin or itraconazole. The overall success rate was 7.1 % point higher in the micafungin group (64.4 vs. 57.3 %, p = 0.404), satisfying the statistical criteria for the non-inferiority of micafungin. The duration of fever and hospital stay were significantly shorter in the micafungin group (6 vs. 7 days, p = 0.014; 22 vs. 27 days, p = 0.033, respectively). Grade 3 adverse events including hyperbilirubinemia (2 vs. 7), elevation of transaminase levels (2 vs. 4), electrolyte imbalance (1 vs. 2), atrial fibrillation (1 vs. 0), and anaphylaxis (1 vs. 0) occurred in 7 and 13 patients in the micafungin (10.4 %) and itraconazole (18.8 %) groups, respectively. Micafungin, when compared with itraconazole, had favorably comparable success rate and toxicity profiles on febrile neutropenia in patients with hematological malignancies. In addition, it showed superior effect on shortening the hospital stay.

Highlights

Febrile neutropenia (FN) is the most common and serious complication that can occur during intensive chemotherapy for patients with hematological malignancies [1, 2]
There was no adverse event-related death in both groups and 3 and 4 patients died of fatal infections in the micafungin and itraconazole group, respectively. This randomized, multicenter trial has shown that empirical micafungin is as effective as itraconazole for patients with febrile neutropenia
The efficacy and safety of the echinocandins as empirical antifungal therapy were demonstrated with caspofungin by Walsh et al [17]

Summary

Introduction

Febrile neutropenia (FN) is the most common and serious complication that can occur during intensive chemotherapy for patients with hematological malignancies [1, 2]. The antifungal drug should be less toxic than amphotericin B and more effective than the azole compounds against Aspergillus and some Candida species other than C. albicans. Micafungin is a novel echinocandin that has shown activity against the Candida and Aspergillus species by inhibiting the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall [9]. Micafungin has shown its possible efficacy and safety as empirical therapy for febrile neutropenic patients in non-randomized studies [10,11,12,13]. There has been no controlled study comparing other antifungal agents with itraconazole for empirical therapy among Koreans. In this study, we prospectively compared clinical outcomes of micafungin with intravenous itraconazole for empirical therapy in febrile neutropenia following anticancer chemotherapy for hematological disorders

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Conclusion