Takaki Yoshikawa1, Satoshi Morita2, Kazuaki Tanabe3, Kazuhiro Nishikawa4, Yuichi Ito5, Takanori Matsui6, Kazumasa Fujitani7, Yutaka Kimura8, Junya Fujita9, Toru Aoyama10, Tsutomu Hayashi10, Haruhiko Cho10, Akira Tsuburaya11, Yumi Miyashita12, Junichi Sakamoto13. 1. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. Electronic address: yoshikawat@kcch.jp. 2. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 3. Department of Gastroenterological and Transplant Surgery, Hiroshima University, Hiroshima, Japan. 4. Department of Surgery, Osaka National Hospital, Osaka, Japan. 5. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. 6. Department of Gastroenterological Surgery, Aichi Cancer Center Aichi Hospital, Okazaki, Japan. 7. Department of Surgery, Osaka General Medical Center, Osaka, Japan. 8. Department of Surgery, Sakai City Medical Center, Sakai, Japan. 9. Department of Surgery, NTT West Osaka Hospital, Osaka, Japan. 10. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. 11. Department of Gastroenterological Surgery, Yokohama City University Medical Center, Yokohama, Japan. 12. Data center, Nonprofit Organization ECRIN, Aichi, Japan. 13. Tokai Central Hospital, Gifu, Japan.
Abstract
BACKGROUND: The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear. PATIENTS AND METHODS: In this 2×2 randomised phase II trial, stage III gastric cancer patients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS). RESULTS:Between October 2009 and July 2011, 83 patients received 2 courses ofSC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses. CONCLUSIONS: Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer. CLINICAL TRIAL NUMBER: UMIN-000002595.
RCT Entities:
BACKGROUND: The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear. PATIENTS AND METHODS: In this 2×2 randomised phase II trial, stage III gastric cancerpatients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS). RESULTS: Between October 2009 and July 2011, 83 patients received 2 courses of SC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses. CONCLUSIONS: Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer. CLINICAL TRIAL NUMBER: UMIN-000002595.