Takayama T, Sato Y, Sagawa T, Okamoto T, Nagashima H, Takahashi Y, Ohnuma H, Kuroiwa G, Miyanishi K, Takimoto R, Matsunaga T, Kato J, Yamaguchi K, Hirata K, Niitsu Y
Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Br J Cancer. 2007 Oct 8;97(7):851-6. doi: 10.1038/sj.bjc.6603957. Epub 2007 Sep 11.
The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.
本剂量递增研究的目的是确定多西他赛、S-1和顺铂联合化疗在不可切除转移性胃癌患者中的最大耐受剂量（MTD）、剂量限制性毒性（DLT）和初步疗效。17例患者在第1 - 14天口服S-1（40mg m(-2)，每日两次），每3周的第8天静脉注射顺铂（60mg m(-2)）和多西他赛（根据DLT情况为60、70或80mg m(-2)）。该联合方案的MTD推测为多西他赛70mg m(-2)。在此剂量水平下，40%的患者（5例中的2例）在第一个疗程中出现4级中性粒细胞减少，20%（5例中的1例）出现3级恶心。因此，多西他赛的推荐剂量定义为60mg m(-2)。DLT为中性粒细胞减少。缓解率（RR）为88.2%（17例中的15例），包括1例完全缓解和14例部分缓解。有2例病情稳定，但无疾病进展。在这15例缓解者中，4例（23.5%）VEGF高表达患者肿瘤迅速消退并实现降期，随后接受了根治性胃切除术。其中3例已无病生存约3年，提示可能已完全治愈。总之，该方案耐受性良好，RR相当高，在转移性胃癌中有可观的降期率。
