Nagata Naoki, Kobayashi Michiya, Kojima Hiroshi, Kondo Ken, Hirabayashi Naoki, Matsui Takanori, Kataoka Masato, Takiyama Wataru, Miyashita Yumi, Nakazato Hiroaki, Araki Kyoujiro, Itoh Hideaki, Nakao Akimasa, Sakamoto Junichi
Department of Surgery 1, University of Occupational and Environmental Health, Japan.
Hepatogastroenterology. 2005 Nov-Dec;52(66):1905-10.
BACKGROUND/AIMS: The present phase I study was planned to define the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of the combination of paclitaxel and cisplatin in patients with advanced or recurrent gastric cancer, and to recommend a dose for the phase II study.
Patients were required to have performance status of 0 to 1, to be between 15 and 74 years of age, and to have adequate organ function. The cisplatin was administered at a fixed dose of 25mg/m2 and paclitaxel was administered at four dose levels (60, 70, 80, and 90mg/m2). Plasma sampling was performed to characterize the pharmacokinetics and pharacodynamics of paclitaxel.
All of the 15 patients entered were assessable for toxicity and response and were subject to analysis of dose-limiting toxicity (DLT) and MTD. Neutropenia (grade 4, for 3 days or more; n=2) indicated DLT at dose level 4 (90mg/m2). The MTD for this regimen was 90mg/m2/week of paclitaxel for 3 weeks. Tumor response occurred in 7 of the 15 patients and the overall response rate was 57.1%. The pharmacokinetic profiles of paclitaxel were similar to those observed after the administration of each dose as a single agent.
Our study demonstrated that the level 3 dosage (80mg/m2 of paclitaxel and 25mg/m2 of cisplatin) is recommended for this combination chemotherapy. This phase I study showed favorable antitumor activity and fewer adverse reactions relative to other types of chemotherapy.
背景/目的：本I期研究旨在确定晚期或复发性胃癌患者中紫杉醇与顺铂联合用药的毒性、最大耐受剂量（MTD）和药代动力学，并为II期研究推荐一个剂量。
患者要求体能状态为0至1，年龄在15至74岁之间，且器官功能良好。顺铂以固定剂量25mg/m²给药，紫杉醇以四个剂量水平（60、70、80和90mg/m²）给药。进行血浆采样以表征紫杉醇的药代动力学和药效学。
入组的15例患者均可评估毒性和反应，并接受剂量限制性毒性（DLT）和MTD分析。中性粒细胞减少（4级，持续3天或更长时间；n = 2）表明在剂量水平4（90mg/m²）时出现DLT。该方案的MTD为紫杉醇90mg/m²/周，共3周。15例患者中有7例出现肿瘤反应，总缓解率为57.1%。紫杉醇的药代动力学特征与单药给药后观察到的相似。
我们的研究表明，该联合化疗推荐3级剂量（紫杉醇80mg/m²和顺铂25mg/m²）。本I期研究显示出良好的抗肿瘤活性，且相对于其他类型的化疗不良反应较少。
