Hiroshi Matsuoka1, Takeshi Yamada2,3, Ryo Ohta4, Yoichiro Yoshida5, Tatsuyuki Watanabe6, Makoto Takahashi7, Chihiro Kosugi8, Atsuko Fukazawa9, Hidekazu Kuramochi10, Akihisa Matsuda4, Hiromichi Sonoda4, Hiroshi Yoshida4, Suguru Hasegawa5, Kazuhiro Sakamoto7, Toshiaki Otsuka11, Keiji Hirata12, Keiji Koda8. 1. Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. 2. Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. y-tak@nms.ac.jp. 3. Department of Surgery, Fujita Health University, Nagoya, Aichi, Japan. y-tak@nms.ac.jp. 4. Department of Surgery, Fujita Health University, Nagoya, Aichi, Japan. 5. Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan. 6. Third Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan. 7. Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan. 8. Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan. 9. Department of Gastroenterological Surgery, Iwata City Hospital, Shizuoka, Japan. 10. Department of Chemotherapy, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan. 11. Deparment of Hygiene and Public Health, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. 12. First Department of Surgery, University of Occupational and Environmental Health, Fukuoka, Japan.
Abstract
BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.
BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.
Authors: Robert J Mayer; Eric Van Cutsem; Alfredo Falcone; Takayuki Yoshino; Rocio Garcia-Carbonero; Nobuyuki Mizunuma; Kentaro Yamazaki; Yasuhiro Shimada; Josep Tabernero; Yoshito Komatsu; Alberto Sobrero; Eveline Boucher; Marc Peeters; Ben Tran; Heinz-Josef Lenz; Alberto Zaniboni; Howard Hochster; James M Cleary; Hans Prenen; Fabio Benedetti; Hirokazu Mizuguchi; Lukas Makris; Masanobu Ito; Atsushi Ohtsu Journal: N Engl J Med Date: 2015-05-14 Impact factor: 91.245
Authors: Axel Grothey; Eric Van Cutsem; Alberto Sobrero; Salvatore Siena; Alfredo Falcone; Marc Ychou; Yves Humblet; Olivier Bouché; Laurent Mineur; Carlo Barone; Antoine Adenis; Josep Tabernero; Takayuki Yoshino; Heinz-Josef Lenz; Richard M Goldberg; Daniel J Sargent; Frank Cihon; Lisa Cupit; Andrea Wagner; Dirk Laurent Journal: Lancet Date: 2012-11-22 Impact factor: 79.321