title: Micafungin for empirical antifungal therapy in patients with febrile neutropenia: multicenter phase 2 study.
abstract: Empirical antifungal therapy is the current standard of care for patients with febrile neutropenia unresponsive to broad-spectrum antimicrobials. Although a number of antifungal agents are currently available, the need remains for effective but less toxic alternatives for this indication. We therefore conducted a phase 2 study of micafungin for 80 patients with hematologic diseases who were suffering from persistent or recurrent fever after at least 96 h of antibacterial therapy. The patients were treated with micafungin at a fixed dose of 150 mg/day. Of the 78 evaluable patients, 54 (69 %) achieved defervescence by the time of neutrophil recovery, and 56 (72 %) completed the treatment in accordance with the provision of the protocol. Four patients developed invasive fungal infection, nine changed antifungal therapy because of lack of efficacy, and three discontinued micafungin because of drug-related adverse events. Based on the composite end point taking account of these, the overall treatment success rate was 60 %, with the lower limit of a 90 % confidence interval (50.3 %) exceeding the predefined threshold success rate (50 %). These findings show the efficacy and safety of micafungin for empirical antifungal therapy in patients with persistent or recurrent febrile neutropenia, warranting further investigation of this drug in a phase 3 study.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizuno
authors.forename: Masashi
authors.initials: M
authors.lastname: Sawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.forename: Mizuho
authors.initials: M
authors.lastname: Shirahata
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Morishita
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tsuzuki
authors.forename: Emi
authors.initials: E
authors.lastname: Goto
authors.forename: Akane
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects*; D064147:Febrile Neutropenia / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000382:microbiology; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin