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OBJECTIVE To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection. PATIENTS AND METHODS A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analysed. RESULTS ACT group obtained markedly improved 3-year PFS [P = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34 to 0.98] and OS than the control group (P = 0.0469; HR for death, 0.56; 95% CI, 0.32 to 0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) (P = 0.02). CONCLUSIONS Additional S-1 chemotherapy may be helpful for improve the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.