1. ¹Department of Gastroenterology, School of Medicine, East Hospital, Kitasato University, Kanagawa, Japan
2. ²Department of Gastrointestinal Oncology/Gastroenterology, National Cancer Center Hospital East, Kashiwa, Japan
3. ³Department of Gastrointestinal Oncology/Gastroenterology, National Cancer Center Hospital, Tokyo, Japan

Correspondence: W Koizumi, E-mail: Koizumi@med.kitasato-u.ac.jp

Received 28 April 2003; Revised 1 September 2003; Accepted 15 September 2003.

Abstract

A dose-escalation study of cisplatin (CDDP) combined with S-1, a new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was given orally at 40 mg m^-2 b.i.d. for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg m^-2 depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg m^-2, because 33.3% of patients (2/6) developed DLTs, mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg m^-2. In the phase II portion, 19 patients including six patients of the RD phase I portion were evaluated. The median administered courses was four (range: 1–8). The incidences of severe (grades 3–4) haematological and nonhaematological toxicities were 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95% confidence interval: 54.9-90.6%), and the median survival day was 383. This regimen is considered to be active against AGC with acceptable toxicity.