Adjuvant treatment with S-1 in patients after R0-resection of adenocarcinoma of the stomach and esophagogastric junction – A multicenter phase I/II feasibility study (GMBH-STO-0114)

Introduction: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. Methods: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30mg/m² bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the common toxicity criteria adverse events 4.0 criteria. Secondary endpoints were one-year relapse-free survival rate, relapse-free survival (RFS) and overall survival (OS). Results: Between 10/2015 and 02/2018, 32 patients were enrolled in 12 German centres and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment due to adverse events (AEs), 7 due to patient’s or investigator’s decision and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m² in 9 patients, and to 20 mg/m² in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥ 3 AEs were neutropenia, diarrhoea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year relapse-free survival rate was 77%. Data on OS were still premature at the end of the study. Conclusion: Adjuvant treatment with S-1 for one year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ cancer after R0-resection.