Phase I/II study of docetaxel (DOC) and S-1 for patients (pts) with advanced gastric cancer (AGC)

Abstract

4064 Background: New combination chemotherapy with DOC and oral DPD-inhibitory fluoropyrimidine, S-1 for pts with AGC was investigated in the multicenter phase I/II study as; 1) agents are active for AGC, 2) different modes of action, and 3) down-regulation of thymidylate synthase by DOC. Methods: Eligibility criteria included; pathologically confirmed AGC, measurable lesions, PS 0–1, ≤1 prior chemotherapy, ≥20 years old, adequate organ functions and written IC. DOC was administered (60–120 min., i.v.) on day 1 and the dose was escalated by 10 mg/m2 from the starting dose of 50mg/m2 in phase I part. S-1 was fixed at the conventional daily dose of 80 mg/m2 on days 1–14. The treatment was repeated every 4 weeks. The recommended dose (RD) of combined DOC+S-1 was studied in every 3–6 pts cohort and determined according to the pre-defined DLTs. 45 pts were planned to enroll at the RD level in phase II part. Results: 50 eligible pts were enrolled in this study from 9/02 to 6/04. In phase I part, all 3 pts enrolled in the starting dose level showed intolerable toxicities (grade 3 neutropenia with infection in one pt and grade 4 neutropenia on day 8 during S-1 administration in 2 pts). Then the dose of DOC was de-escalated to 40 mg/m2 and this dose level was determined as RD for phase II part. 46 out of 47 pts enrolled were evaluable for safety and 44 pts for efficacy, respectively. Pt characteristics were as follows; median age 65 (range 42–79), M/F 31/15, PS0/1 26/20, histological type differentiated/undifferentiated 29/17 and chemonaïve/pre-treated 25/21 pts. 9 pre-treated pts (45%) and 12 chemonaïve pts (50%) showed response (RECIST). Overall response rate was 48% (95%CI: 33–63%). Pts received a median of 3 courses (range 1–6). Common grade 3+ toxicities were neutropenia (70%), leucopenia (39%), anemia (22%), and anorexia (20%). These toxicities were tolerable and manageable. No treatment-related death was observed. Preliminary survival analyses showed an estimated median survival of 377 days (95%CI: 266–488 days). Matured survival data will be presented at the meeting. Conclusions: This new regimen with DOC and S-1 showed promising activity and manageable toxicity, thereby leading to a further phase III study with this regimen in pts with AGC. No significant financial relationships to disclose.