Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Int J Hematol. 2013 Aug;98(2):231-6. doi: 10.1007/s12185-013-1396-7. Epub 2013 Jul 16.
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.
经验性抗真菌治疗是目前发热性中性粒细胞减少症对广谱抗菌药物无反应患者的标准治疗方法。尽管目前有许多抗真菌药物可供选择,但对于这种适应症,仍然需要有效但毒性较低的替代品。因此,我们对 80 名患有血液疾病的患者进行了米卡芬净的 2 期研究,这些患者在接受至少 96 小时的抗菌治疗后仍持续或反复发热。患者接受米卡芬净固定剂量 150mg/天治疗。在 78 名可评估患者中,54 名(69%)在中性粒细胞恢复时退热,56 名(72%)按照方案规定完成治疗。4 名患者发生侵袭性真菌感染,9 名因疗效不佳而改变抗真菌治疗,3 名因药物相关不良反应而停用米卡芬净。根据综合终点考虑这些因素,总体治疗成功率为 60%,90%置信区间(50.3%)下限超过预设的成功率(50%)阈值。这些发现表明米卡芬净在治疗持续性或复发性发热性中性粒细胞减少症患者的经验性抗真菌治疗中的疗效和安全性,值得进一步在 3 期研究中研究该药物。