Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol®-PM) in patients with solid tumors
Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol®-PM) in patients with solid tumors
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DOI：
10.1093/annonc/mdp315
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发表时间：
2010-02-01
影响因子：
50.5
通讯作者：
Chowbay, B.
中科院分区：
文献类型：
--
作者：
Lim, W. T.;Tan, E. H.;Chowbay, B.
背景：本研究的目的是确定Genexol-PM在亚洲癌症患者中的最大耐受剂量（MTD）和药代动力学特征。材料与方法：既往化疗难治性患者（N = 24）给予Genexol-PM每周一次输注1小时，连续3周，然后休息一周。起始剂量为80 mg/m(2)，最大给药剂量为200 mg/m(2)。结果：大多数患者患有肺癌、鼻咽癌和乳腺癌，其中11名患者（46%）先前以紫杉烷为基础的化疗失败。MTD定义为180 mg/m(2)。第1周期最常见的3级非血液学不良事件是疲劳（4%）和神经病变（4%），主要发生在200 mg/m(2)的剂量下。5例（21%）患者部分缓解，9例（38%）患者病情稳定，7例（29%）患者病情进展。11例先前紫杉烷难治性患者中有5例显示Genexol-PM的临床获益。Genexol-PM的药代动力学表现出剂量正比关系，随着Genexol-PM剂量从80 mg/m增加到200 mg/m，最大浓度（C-max）和浓度-时间曲线下从0到无穷远的面积（AUC（0-无穷远））分别增加约4倍和3倍(2)。所有患者对Genexol-PM的中位全身清除率为43.9 l/h。结论：Genexol-PM每周方案耐受性良好，并且在难治性肿瘤患者中观察到反应，包括先前紫杉烷类化疗失败的患者。
Background: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients.Materials and methods: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m(2) and the maximum administered dose was 200 mg/m(2).Results: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m(2). The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m(2). Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C-max) and the area under the concentration-time curve from zero to infinity (AUC(0-infinity)) increasing by approximately four-and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m(2). The median total-body clearance of Genexol-PM for all patients was 43.9 l/h.Conclusion: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.