A phase I/II study of S-1 and CPT-11 therapy for patients (pts) with metastatic gastric carcinoma (GC)

Abstract

14156 Background: S-1 was recently developed as a first line chemotherapy for the treatment of metastatic GC. We performed a phase I study of S-1 plus CPT-11 therapy for metastatic GC and reported that the maximum tolerated dose and the recommended dose (RD) of CPT-11 were 90 and 80 mg/m2, respectively. Objectives of the present trial were to estimate the response rate (RR) of this regimen. Methods: Eligibility criteria were as follows; histologically proven CRC with measurable metastatic lesions, PS 0–2, age < 80, adequate organ functions, and written informed consent. No prior chemotherapy except adjuvant setting was allowed. S-1 was administered orally, 80 mg/m2/day on 14 consecutive days with 14 days’ rest for 4 weeks, and CPT-11 was infused at the RD in phase I trial on days 1 and 8. This schedule was repeated every 4 weeks. Results: Objective responses according to RECIST criteria were observed in 26 of the 42 pts (RR = 62%). Nineteen pts were with Grade 3 and 4 neutropenia and 10 with diarrhea Median survival time was 444 days. Intratumoral gene expression was analyzed using laser capture microdissection and RT-PCR method (Response Genetic Inc). Lower gene expression was observed in tumor cell of responder (P = 0.01). Conclusions: High RR and mild toxicity profile of S-1 plus biweekly CPT-11 therapy may be favorable for metastatic GC. No significant financial relationships to disclose.