1. ¹Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Japan
2. ²Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan
3. ³Department of Internal Medicine, Higashi Sapporo Hospital, Sapporo, Japan
4. ⁴First Department of Surgery, Sapporo Medical University, School of Medicine, Sapporo, Japan

Correspondence: Dr T Takayama, E-mail: ttakayam@sapmed.ac.jp

Received 31 May 2007; Revised 23 July 2007; Accepted 8 August 2007; Published online 11 September 2007.

Abstract

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.