一项关于S-1联合纳米白蛋白结合型紫杉醇治疗不可切除或复发性胃癌患者的I期研究。
A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer.
作者信息
Nakayama Norisuke, Ishido Kenji, Chin Keisho, Nishimura Ken, Azuma Mizutomo, Matsusaka Satoshi, Inokuchi Yasuhiro, Tanabe Satoshi, Kumekawa Yosuke, Koizumi Wasaburo
机构信息
Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan.
Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan.
出版信息
Gastric Cancer. 2017 Mar;20(2):350-357. doi: 10.1007/s10120-016-0614-4. Epub 2016 May 17.
BACKGROUND
In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study.
METHODS
The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m on day 1 or 8.
RESULTS
Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m twice daily plus nab-paclitaxel 220 mg/m on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m twice daily plus nab-paclitaxel 260 mg/m on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone.
CONCLUSIONS
Based on the present results, the RD was determined as level 3a (S-1 80 mg/m twice daily plus nab-paclitaxel 260 mg/m on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer.
背景
在日本，口服氟尿嘧啶类药物S-1联合顺铂是晚期胃癌的标准治疗方案，而纳米白蛋白结合型紫杉醇也是一种治疗选择。我们旨在通过一项1期研究评估S-1联合纳米白蛋白结合型紫杉醇在晚期胃癌患者中的耐受性、药代动力学、安全性和临床疗效。
方法
主要目的是确定S-1联合纳米白蛋白结合型紫杉醇的最大耐受剂量（MTD）和推荐剂量（RD）。该研究按照标准的3+3方法设计。患者接受为期3周的治疗周期。S-1口服给药，剂量为80mg/m²，每日两次，共14天，纳米白蛋白结合型紫杉醇在第1天或第8天静脉输注，剂量为180、220或260mg/m²。
结果
在入组的16例患者中，1例患者在2a级（S-1 80mg/m²每日两次加纳米白蛋白结合型紫杉醇220mg/m²在第1天）出现剂量限制性毒性。未得出MTD，但确定RD为3a级（S-1 80mg/m²每日两次加纳米白蛋白结合型紫杉醇260mg/m²在第1天）。最常见的3-4级毒性是中性粒细胞减少（62.5%）。总缓解率为54.5%。联合使用的S-1和紫杉醇的药代动力学特征与单独使用纳米白蛋白结合型紫杉醇或S-1时相当。
结论
基于目前的结果，确定RD为3a级（S-1 80mg/m²每日两次加纳米白蛋白结合型紫杉醇260mg/m²在第1天）。这种联合治疗耐受性良好，在晚期胃癌患者中显示出抗肿瘤疗效。
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