Phase I dose-finding study of epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer (AGC).

Abstract

123 Background: To determine the recommended dose (RD) and dose-limiting toxicity (DLT) of EOS combination in patients with previously untreated AGC. Methods: Previously untreated patients with histologically proven metastatic or recurrent AGC and ECOG performance status 0-2 were enrolled. Fixed dose of epirubicin (50 mg/m2) and oxaliplatin (130 mg/m2) was administered i.v. on day 1. The dose of S-1 was escalated as following schedule: Level I: 30 mg/m2, Level II: 40 mg/m2, Level III: 45 mg/m2, Level IV: 50 mg/m2. S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment. Results: Nineteen patients were enrolled: 13 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 53 years (range, 40-71 years). At dose level II, 1 DLT (grade 4 neutropenia lasting more than 5 days) was found among 6 patients while at dose level III, 2 DLTs (grade 3 diarrhea and nausea) were observed among 4 patients. Therefore, the dose level II was determined as RD. Cumulative (all cycles) grade 3/4 toxicity included neuropenia (58%), leucopenia (32%), thrombocytopenia (11%), diarrhea (11%), and nausea (5%). Of 13 patients with measurable lesions, 8 achieved partial response and 3 showed stable diseases, and the objective response rate was 62% (95% CI, 36-88%). The median progression-free survival was 6.5 months (95% CI, 4.7-8.2 months). Conclusions: The RD of the EOS regimen in patients with previously untreated AGC was epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 on day 1 and S-1 40 mg/m2 twice a day on days 1-14 of every 21-day cycle. This regimen seems to have promising preliminary activity. No significant financial relationships to disclose.