Department of Medical Oncology.
Biostatistic Unit, Division of Clinical Trials and Epidemiological Sciences.
Ann Oncol. 2010 Feb;21(2):382-388. doi: 10.1093/annonc/mdp315. Epub 2009 Jul 24.
The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients.
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).
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.
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.
本研究旨在确定 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。
24 例既往化疗耐药的患者每周接受 1 小时输注 Genexol-PM，连续 3 周，然后休息 1 周。起始剂量为 80mg/m²，最大给药剂量为 200mg/m²。
大多数患者患有肺癌、鼻咽癌和乳腺癌，11 例患者（46%）曾接受过紫杉烷类化疗失败。MTD 定义为 180mg/m²。第 1 周期最常见的 3 级非血液学不良事件为乏力（4%）和神经病变（4%），主要发生在 200mg/m²时。5 例（21%）患者有部分缓解，9 例（38%）患者病情稳定，7 例（29%）患者病情进展。在 11 例先前紫杉烷类耐药的患者中，有 5 例对 Genexol-PM 显示出临床获益。Genexol-PM 的药代动力学呈剂量比例关系，当 Genexol-PM 的剂量从 80mg/m²增加到 200mg/m²时，最大浓度（C(max)）和从 0 到无穷大的浓度-时间曲线下面积（AUC(0-infinity)）分别增加约 4 倍和 3 倍。所有患者的 Genexol-PM 总体清除率中位数为 43.9l/h。
Genexol-PM 的每周方案耐受性良好，在包括先前接受过紫杉烷类化疗失败的耐药肿瘤患者中观察到了应答。
