Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin.
Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin.
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DOI：
10.1038/sj.bjc.6602204
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发表时间：
2004-11-15
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
NK911是一种新型超分子纳米载体，旨在增强阿霉素（DXR）的递送，并且是在小鼠实体瘤中表现出有效积累的成功聚合物胶束系统之一。本研究的目的是确定 NK911 的最大耐受剂量 (MTD) 和剂量限制毒性 (DLT)，并评估其在人体中的药代动力学特征。每3周使用输液泵以10mg DXR当量min−1的速率向实体瘤患者静脉注射NK911。起始剂量为6mg DXR当量 m−2，并根据加速滴定法逐步递增剂量。共有 23 名患者参与了这项研究。中性粒细胞减少症是主要的血液学毒性，50 和 67mgm−2 剂量时观察到 3 级或 4 级中性粒细胞减少症。 Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia.在研究的剂量确定部分，在 67mgm−2 的剂量下观察到 DLT（4 级中性粒细胞减少症持续超过 5 天）。 Thus, this dosage level was determined to be the MTD.在任何情况下均未观察到输注相关反应。 The C5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics.在 23 名患者中，一名转移性胰腺癌患者获得部分缓解。 NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages.推荐的II期剂量确定为每3周50mgm−2。
NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min−1. The starting dose was 6 mg DXR equivalent m−2, and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m−2. Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m−2 (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m−2 every 3 weeks.
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影响因子：
45.3
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