Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study

• Published in: European journal of cancer (1990) 2013-11, Vol.49 (17), p.3616-3624
• Main Authors: Ajani, J.A, Buyse, M, Lichinitser, M, Gorbunova, V, Bodoky, G, Douillard, J.Y, Cascinu, S, Heinemann, V, Zaucha, R, Carrato, A, Ferry, D, Moiseyenko, V
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adenocarcinoma - drug therapy; Adenocarcinoma - epidemiology; Adenocarcinoma - mortality; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Disease Progression; Drug Combinations; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - epidemiology; Esophageal Neoplasms - mortality; Female; FLAGS; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Gastric; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Phase 3; S-1; Stomach Neoplasms - drug therapy; Tegafur - administration & dosage; Tegafur - adverse effects; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.07.003

Abstract Background The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies. Patients and methods A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses. Results Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80–1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand–foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P < 0.047). Conclusion CS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.