Cancer Chemother Pharmacol. 2014 Jun;73(6):1173-9. doi: 10.1007/s00280-014-2452-6.
Polymeric micelle-formulated paclitaxel (PM paclitaxel) is a nanoscale drug delivery compound. This study investigated the maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetic (PK) profile of PM paclitaxel in Chinese patients with treatment-refractory advanced or relapsed solid tumors.
Dose escalation of PM paclitaxel followed the standard ‘3 + 3’ rule, starting at 175 mg/m(2). PM paclitaxel was administered over 3 h every 3 weeks. Patients were treated until disease progression, intolerance, death, or consent withdrawal. Blood samples were collected for PK testing.
A ll 23 patients were evaluable for toxicity. Neutropenia,neuropathy, and myalgia were the most common toxicities; acute hypersensitivity reaction was not observed. One of six patients at dose level 4 (350 mg/m(2)) and two of six patients at dose level 5 (390 mg/m(2)) developed grade 4 neutropenia. The MTD was 350 mg/m(2). No patients discontinued treatment because of neuropathy. Partial response was seen in five of 20 patients (25 %) who had response assessment, three of whom had prior exposure to taxanes (two were heavily pretreated). Ten patients (50 %)had stable disease at cycle 2 and only five patients (25 %) had disease progression. The area under the curve and the maximum concentration of paclitaxel increased with escalating doses, suggesting that PM paclitaxel has linear PKs.
The main dose-limiting toxicity for PM paclitaxel was neutropenia, and the recommended dose for phase II study is 300 mg/m(2). PM paclitaxel is superior to conventional paclitaxel for its simplified premedication regimen and delivery of a higher paclitaxel dose without increased neuropathy.
聚合物胶束剂型紫杉醇（PM 紫杉醇）是一种纳米级药物递送化合物。本研究旨在探讨 PM 紫杉醇在治疗耐药性晚期或复发性实体瘤的中国患者中的最大耐受剂量（MTD）、剂量限制毒性和药代动力学（PK）特征。
PM 紫杉醇的剂量递增采用标准的“3+3”规则，起始剂量为 175mg/m2。PM 紫杉醇每 3 周给药一次，每次 3 小时。患者持续治疗至疾病进展、不耐受、死亡或同意退出。采集血样进行 PK 检测。
所有 23 例患者均可进行毒性评估。中性粒细胞减少症、神经病变和肌痛是最常见的毒性反应；未观察到急性过敏反应。在 350mg/m2 剂量水平的 6 例患者中有 1 例（17%）和 390mg/m2 剂量水平的 6 例患者中有 2 例（33%）发生 4 级中性粒细胞减少症。MTD 为 350mg/m2。无患者因神经病变而停止治疗。在 20 例可评估疗效的患者中有 5 例（25%）出现部分缓解，其中 3 例先前接受过紫杉烷类药物治疗（2 例为重度预处理）。10 例患者（50%）在第 2 周期时疾病稳定，仅有 5 例（25%）疾病进展。随着剂量递增，紫杉醇的曲线下面积和最大浓度增加，提示 PM 紫杉醇具有线性 PK 特征。
PM 紫杉醇的主要剂量限制毒性为中性粒细胞减少症，II 期研究的推荐剂量为 300mg/m2。PM 紫杉醇与普通紫杉醇相比，其预处理方案简化，可给予更高剂量的紫杉醇而不增加神经病变。
