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Micafungin for empirical antifungal therapy in patients with febrile neutropenia: multicenter phase 2 study

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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.

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Acknowledgments

We thank Ms. Mio Kurata and Ms. Shizuka Kobayashi for their administrative support. This study was supported by the Center for Supporting Hematology–Oncology Trials (C-SHOT).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Hiroki Mizuno, Masamitsu Yanada, Yukiyasu Ozawa, Emi Goto, Akane Tsujimura & Tomoki Naoe

  2. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Hiroki Mizuno, Masashi Sawa, Mizuho Shirahata, Tomonori Kato & Takanobu Morishita

  3. Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan

    Masamitsu Yanada, Masato Watanabe, Motohiro Tsuzuki & Nobuhiko Emi

  4. Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Hirokazu Nagai & Tomoki Naoe

  5. Depertment of HSCT Data Management, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Ritsuro Suzuki & Yoshiko Atsuta

Authors
  1. Hiroki Mizuno
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  2. Masashi Sawa
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  3. Masamitsu Yanada
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  4. Mizuho Shirahata
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  6. Tomonori Kato
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  7. Hirokazu Nagai
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  8. Yukiyasu Ozawa
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  9. Takanobu Morishita
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  10. Motohiro Tsuzuki
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  11. Emi Goto
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  12. Akane Tsujimura
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  13. Ritsuro Suzuki
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  14. Yoshiko Atsuta
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  15. Nobuhiko Emi
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  16. Tomoki Naoe
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Corresponding author

Correspondence to Masamitsu Yanada.

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Mizuno, H., Sawa, M., Yanada, M. et al. Micafungin for empirical antifungal therapy in patients with febrile neutropenia: multicenter phase 2 study. Int J Hematol 98, 231–236 (2013). https://doi.org/10.1007/s12185-013-1396-7

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  • DOI: https://doi.org/10.1007/s12185-013-1396-7

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