Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naive Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial

Background. We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S-1 plus cisplatin for first-line treatment of human epidermal growth receptor 2 (HER2)-negative advanced gastric cancer in Japan. Methods. Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m(2) twice daily for 14 days plus cisplatin at 80 mg/m(2) on day 1 every 3 weeks (n = 43) or S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m(2) on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate. Results. Response rate did not differ significantly between the capecitabine-cisplatin and S-1-cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S-1-cisplatin tended to confer a better progression-free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine-cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine-cisplatin group. Conclusion. Capecitabine-cisplatin failed to demonstrate superior efficacy compared with S-1-cisplatin. The higher incidence of severe adverse events with capecitabine-cisplatin suggests that S-1-cisplatin should remain the standard first-line chemotherapy for HER2-negative advanced gastric cancer in Japan.