Phase I/II study of irinotecan (CPT-11) and S-1 in the treatment of advanced gastric cancer.

A phase I/II study to determine the recommended dose for combination therapy with CPT-11 (irinotecan hydrochloride) and S-1 (tegafur, gimestat and otastat potassium) for advanced or recurrent gastric cancer, and to assess the safety and efficacy of this therapy. In the phase I portion of the study, S-1 was administered from day 1 to 14 at a fixed dose approved in Japan (80 mg/m2/day), and CPT-11 was administered on days 1 and 8, with its dose being escalated to 100 from 80 mg/m2. This regimen was repeated at 3-week intervals. The phase II portion of the study assessed the efficacy and safety of this regimen at the recommended dose determined in the phase I portion of the study. Seven patients were enrolled in the phase I portion of the study. The dose-limiting toxicity was the delay of administration owing to adverse reactions (leucopenia and diarrhea). The maximum tolerated dose of CPT-11 was 100 mg/m2 and the recommended dose was determined to be 80 mg/m2. In the phase II portion of the study, 10 patients with no prior chemotherapy regimen were enrolled. The median number of treatment cycles given was 4.5, the response rate was 20.0% (2/10) in all patients, the tumor control rate stable disease or better response was 60% (6/10) and the mean survival time was 311 days. Major adverse reactions included a decreased hemoglobin level, diarrhea, nausea and anorexia of grade 3 or worse (each occurred in 10% of the patients). Other adverse reactions were slight and well tolerated. The present combination therapy with CPT-11 and S-1 produced a low response rate but a high tumor control rate (stable disease or better response) and slight prolongation of survival time. This is a well-tolerated ambulatory regimen for advanced gastric cancer.