索拉非尼联合卡培他滨和顺铂一线治疗晚期胃癌的 I 期剂量探索研究。
Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer.
机构信息
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, South Korea.
出版信息
Invest New Drugs. 2012 Feb;30(1):306-15. doi: 10.1007/s10637-010-9531-2. Epub 2010 Sep 14.
BACKGROUND
To define maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer (AGC) patients.
METHODS
Four dose-level combinations were tested in a standard 3 + 3 dose escalation design. Level 1: sorafenib 400 mg/d, capecitabine 1,600 mg/m(2)/d, cisplatin 80 mg/m(2). Level 2: sorafenib 800 mg/d, capecitabine 1,600 mg/m(2)/d, cisplatin 80 mg/m(2). Level 3: sorafenib 800 mg/d, capecitabine 2,000 mg/m(2)/d, cisplatin 80 mg/m(2). Level 1A: sorafenib 800 mg/d, capecitabine 1,600 mg/m(2)/d, cisplatin 60 mg/m(2).
RESULTS
There were 1 DLT at Level 2, and 2 DLTs at Level 3 (Level 3 was MTD). Since the relative dose intensity (RDI) of sorafenib and capecitabine could not be maintained at Level 2, Level 1A was newly investigated. As no DLT was observed and RDI remained above 80%, Level 1A is the recommended dose for the next clinical trial. Objective response rate was 62.5% (10 of 16 patients, 95% CI; 38.8-86.2%). Median progression-free survival and overall survival were 10.0 months (95% CI; 7.4-13.8) and 14.7 months (95% CI; 12.0-20.0), respectively.
CONCLUSIONS
Sorafenib 400 mg bid daily, capecitabine 800 mg/m(2) bid (days 1-14), and cisplatin 60 mg/m(2) (day 1) is recommended for further development in AGC.
背景
旨在确定索拉非尼联合卡培他滨/顺铂治疗晚期胃癌（AGC）患者的最大耐受剂量（MTD）、剂量限制毒性（DLT）和初步疗效。
方法
采用标准的 3+3 剂量递增设计，对 4 个剂量水平组合进行了测试。第 1 水平：索拉非尼 400mg/d，卡培他滨 1600mg/m2/d，顺铂 80mg/m2。第 2 水平：索拉非尼 800mg/d，卡培他滨 1600mg/m2/d，顺铂 80mg/m2。第 3 水平：索拉非尼 800mg/d，卡培他滨 2000mg/m2/d，顺铂 80mg/m2。第 1A 水平：索拉非尼 800mg/d，卡培他滨 1600mg/m2/d，顺铂 60mg/m2。
结果
第 2 水平出现 1 例 DLT，第 3 水平出现 2 例 DLT（第 3 水平为 MTD）。由于第 2 水平时索拉非尼和卡培他滨的相对剂量强度（RDI）无法维持，因此新研究了第 1A 水平。由于未观察到 DLT，且 RDI 保持在 80%以上，因此推荐第 1A 水平作为下一临床试验的剂量。客观缓解率为 62.5%（16 例患者中有 10 例，95%CI；38.8-86.2%）。中位无进展生存期和总生存期分别为 10.0 个月（95%CI；7.4-13.8）和 14.7 个月（95%CI；12.0-20.0）。
结论
推荐索拉非尼 400mg bid 每日、卡培他滨 800mg/m2 bid（第 1-14 天）和顺铂 60mg/m2（第 1 天）用于进一步治疗 AGC。
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