1. ¹Department of Esophagogastric Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo 113-8519, Japan
2. ²Mutsugi Clinic, 1-4-14, Mutsugi, Adachi-ku, Tokyo 121-0052, Japan
3. ³Department of Digestive and General Surgery, Saitama Medical School, 38, Moro-Hongo, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan
4. ⁴Tojun Hospital 4-3-4, Hitotsuya, Adachi, Tokyo 121-0075, Japan
5. ⁵Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo, Tokyo 113-8519, Japan

Correspondence: Dr M Inokuchi, E-mail: m-inokuchi.srg2@tmd.ac.jp

Received 16 December 2005; Revised 13 February 2006; Accepted 15 February 2006; Published online 28 March 2006.

Abstract

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an 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 administered orally at 80 mg m^-2 day^-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m^-2 day^-1, stepping up to 100 mg m^-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m^-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m^-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m^-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1–13). The incidences of severe (grade 3–4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2–76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.