C Morizane1, T Okusaka2, J Mizusawa3, H Katayama3, M Ueno4, M Ikeda5, M Ozaka6, N Okano7, K Sugimori8, A Fukutomi9, H Hara10, N Mizuno11, H Yanagimoto12, K Wada13, K Tobimatsu14, K Yane15, S Nakamori16, H Yamaguchi17, A Asagi18, S Yukisawa19, Y Kojima20, K Kawabe21, Y Kawamoto22, R Sugimoto23, T Iwai24, K Nakamura25, H Miyakawa26, T Yamashita27, A Hosokawa28, T Ioka29, N Kato30, K Shioji31, K Shimizu32, T Nakagohri33, K Kamata34, H Ishii35, J Furuse7. 1. Department of Hepatobiliary and Pancreatic Oncology, Tokyo. Electronic address: cmorizan@ncc.go.jp. 2. Department of Hepatobiliary and Pancreatic Oncology, Tokyo. 3. JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo. 4. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama. 5. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa. 6. Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo. 7. Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo. 8. Gastroenterological Center, Yokohama City University Medical Center, Yokohama. 9. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka. 10. Department of Gastroenterology, Saitama Cancer Center, Saitama. 11. Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya. 12. Department of Surgery, Kansai Medical University Hospital, Hirakata. 13. Department of Surgery, Teikyo University School of Medicine, Tokyo. 14. Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine, Kobe. 15. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo. 16. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka. 17. Department of Clinical Oncology, Jichi Medical University, Shimotsuke. 18. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama. 19. Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya. 20. Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo. 21. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka. 22. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo. 23. Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka. 24. Department of Gastroenterology, Kitasato University Hospital, Sagamihara. 25. Division of Gastroenterology, Chiba Cancer Center, Chiba. 26. Department of Bilio-Pancreatology, Sapporo Kousei General Hospital, Sapporo. 27. Department of Gastroenterology, Kanazawa University, Kanazawa. 28. Department of Gastroenterology and Hematology, University of Toyama, Faculty of Medicine, Toyama. 29. Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka. 30. Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba. 31. Department of Internal medicine, Niigata Cancer Center Hospital, Niigata. 32. Department of Gastroenterology, Tokyo Women's Medical University, Tokyo. 33. Gastroenterological Surgery, Tokai University School of Medicine, Isehara. 34. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka. 35. Clinical Research Center, Chiba Cancer Center, Chiba, Japan.
Abstract
BACKGROUND:Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS:Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.
RCT Entities:
BACKGROUND:Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS:GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.
Authors: Avani Athauda; Caroline Fong; David K Lau; Milind Javle; Ghassan K Abou-Alfa; Chigusa Morizane; Keith Steward; Ian Chau Journal: Cancer Treat Rev Date: 2020-03-12 Impact factor: 12.111
Authors: Yi Yu; Shanshan Huang; Jun Chen; Feng Yu; Lin Zhang; Xiaojun Xiang; Jun Deng; Ziling Fang; Junhe Li; Jianping Xiong Journal: Cancer Control Date: 2021 Jan-Dec Impact factor: 3.302