Phase I/II study of CPT-11 plus S-1 in patients with advanced gastric cancer

Abstract

4191 Background: We reported the results of phase I study part of the treatment with CPT-11 (irinotecan) and S-1, a new oral fluoropyrimidine, in gastric cancer patients at ASCO 2002. This paper reports Phase II study part using the previously defined recommended dose, including results of median survival time (MST). Methods: A combined treatment of CPT-11 and S-1 was performed in patients with inoperable advanced gastric cancer who had not received a prior chemotherapy. S-1 was orally administered twice a day for 14 consecutive days, and CPT-11 was administered as a 90-minute intravenous infusion on days 1 and 15. This schedule was repeated every 4 weeks. The patients received 80 mg/m2 /day dose of S-1 and 125 mg/m2 of CPT-11 recommended from phase I study. Results: Fifteen patients were registered in this Phase I study. And 9 patients were added in this Phase II study. Non-hematological toxicities were almost classified as grade 2 or lower, except for grade 3 nausea and grade 3 dermatitis at level 2. These adverse events were manageable by administering antiemetic drugs and drug rest. As for hematological toxicities, grade 4 neutropenia occurred in one patient at level 1 and level 2 at Phase I. And grade 4 neutropenia occurred in four patients at level 2 of Phase II. However, they recovered after the drug rest, and we could continue the administration based on the standard for dose modifications. These side effects were tolerable, and did not impede the schedule. An overall response rate was 54.2%. MST of this regimen is 581 days. Tissue typing MST was superior in significance in the well-differentiated type adenocarcinoma that was being undifferentiated type adenocarcinoma 450 days (95%CI 376 -936 day) for well-differentiated type adenocarcinoma 656 days (95%CI 227–673 days, P =0.04 logrank). Discussion: The results indicate that this combined treatment is applicable to outpatient treatments. MST of the therapy is 581 days meaningful results for this type of patients setting. The severities of adverse events differ individually, but manageable by carefully observing the patients and proper dose modifications. The updated analysis will be presented at the meeting. No significant financial relationships to disclose.