Akira Tsuburaya1, Kazuhiro Yoshida2, Michiya Kobayashi3, Shigefumi Yoshino4, Masazumi Takahashi5, Nobuhiro Takiguchi6, Kazuaki Tanabe7, Naoto Takahashi8, Hiroshi Imamura9, Naokuni Tatsumoto10, Akinori Hara11, Kazuhiro Nishikawa12, Ryoji Fukushima13, Isao Nozaki14, Hiroshi Kojima15, Yumi Miyashita16, Koji Oba17, Marc Buyse18, Satoshi Morita19, Junichi Sakamoto20. 1. Yokohama City University, Yokohama, Japan. 2. Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: kyoshida@gifu-u.ac.jp. 3. Department of Human Health and Medical Sciences, Kochi Medical School, Nankoku, Japan. 4. Yamaguchi University Graduate School of Medicine, Ube, Japan. 5. Yokohama Municipal Citizen's Hospital, Yokohama, Japan. 6. Chiba Cancer Centre, Chiba, Japan. 7. Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. 8. Jikei University Hospital, Tokyo, Japan. 9. Sakai Municipal Hospital, Sakai, Japan. 10. Miyoshi Central Hospital, Miyoshi, Japan. 11. Saiseikai Suita Hospital, Suita, Japan. 12. Osaka General Medical Centre, Osaka, Japan. 13. Teikyo University School of Medicine, Tokyo, Japan. 14. National Hospital Organization Shikoku Cancer Centre, Matsuyama, Japan. 15. Aichi Cancer Centre Aichi Hospital, Okazaki, Japan. 16. NPO Epidemiological and Clinical Research Information Network, Okazaki, Japan. 17. Translational Research and Clinical Trial Centre, Hokkaido University Hospital, Sapporo, Japan. 18. International Drug Development Institute, Louvain-la-Neuve, Belgium. 19. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 20. Tokai Central Hospital, Kakamigahara, Japan.
Abstract
BACKGROUND: The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. METHODS: We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m(2) per day), S-1 only (80 mg/m(2) per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m(2)) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. FINDINGS: We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). INTERPRETATION: Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. FUNDING: Epidemiological and Clinical Research Information Network.
RCT Entities:
BACKGROUND: The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. METHODS: We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m(2) per day), S-1 only (80 mg/m(2) per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m(2)) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. FINDINGS: We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). INTERPRETATION: Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. FUNDING: Epidemiological and Clinical Research Information Network.
Authors: Catherine Timmermans; Erik Doffagne; David Venet; Lieven Desmet; Catherine Legrand; Tomasz Burzykowski; Marc Buyse Journal: Gastric Cancer Date: 2015-08-23 Impact factor: 7.370
Authors: Michael K Gibson; Paul Catalano; Lawrence R Kleinberg; Charles A Staley; Elizabeth A Montgomery; Antonio Jimeno; Wei Frank Song; Mary F Mulcahy; Lawrence P Leichman; Al B Benson Journal: Oncologist Date: 2019-06-21
Authors: Nelson Adami Andreollo; Eric Drizlionoks; Valdir Tercioti-Junior; João de Souza Coelho-Neto; José Antonio Possato Ferrer; José Barreto Campello Carvalheira; Luiz Roberto Lopes Journal: Arq Bras Cir Dig Date: 2019-12-20