PMID- 31566666 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 30 IP - 12 DP - 2019 Dec 1 TI - Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. PG - 1950-1958 LID - S0923-7534(20)32557-6 [pii] LID - 10.1093/annonc/mdz402 [doi] AB - 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-naive 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 alpha 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. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Morizane, C AU - Morizane C AD - Department of Hepatobiliary and Pancreatic Oncology, Tokyo. Electronic address: cmorizan@ncc.go.jp. FAU - Okusaka, T AU - Okusaka T AD - Department of Hepatobiliary and Pancreatic Oncology, Tokyo. FAU - Mizusawa, J AU - Mizusawa J AD - JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo. FAU - Katayama, H AU - Katayama H AD - JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo. FAU - Ueno, M AU - Ueno M AD - Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama. FAU - Ikeda, M AU - Ikeda M AD - Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa. FAU - Ozaka, M AU - Ozaka M AD - Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo. FAU - Okano, N AU - Okano N AD - Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo. FAU - Sugimori, K AU - Sugimori K AD - Gastroenterological Center, Yokohama City University Medical Center, Yokohama. FAU - Fukutomi, A AU - Fukutomi A AD - Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka. FAU - Hara, H AU - Hara H AD - Department of Gastroenterology, Saitama Cancer Center, Saitama. FAU - Mizuno, N AU - Mizuno N AD - Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya. FAU - Yanagimoto, H AU - Yanagimoto H AD - Department of Surgery, Kansai Medical University Hospital, Hirakata. FAU - Wada, K AU - Wada K AD - Department of Surgery, Teikyo University School of Medicine, Tokyo. FAU - Tobimatsu, K AU - Tobimatsu K AD - Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine, Kobe. FAU - Yane, K AU - Yane K AD - Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo. FAU - Nakamori, S AU - Nakamori S AD - Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka. FAU - Yamaguchi, H AU - Yamaguchi H AD - Department of Clinical Oncology, Jichi Medical University, Shimotsuke. FAU - Asagi, A AU - Asagi A AD - Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama. FAU - Yukisawa, S AU - Yukisawa S AD - Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya. FAU - Kojima, Y AU - Kojima Y AD - Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo. FAU - Kawabe, K AU - Kawabe K AD - Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka. FAU - Kawamoto, Y AU - Kawamoto Y AD - Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo. FAU - Sugimoto, R AU - Sugimoto R AD - Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka. FAU - Iwai, T AU - Iwai T AD - Department of Gastroenterology, Kitasato University Hospital, Sagamihara. FAU - Nakamura, K AU - Nakamura K AD - Division of Gastroenterology, Chiba Cancer Center, Chiba. FAU - Miyakawa, H AU - Miyakawa H AD - Department of Bilio-Pancreatology, Sapporo Kousei General Hospital, Sapporo. FAU - Yamashita, T AU - Yamashita T AD - Department of Gastroenterology, Kanazawa University, Kanazawa. FAU - Hosokawa, A AU - Hosokawa A AD - Department of Gastroenterology and Hematology, University of Toyama, Faculty of Medicine, Toyama. FAU - Ioka, T AU - Ioka T AD - Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka. FAU - Kato, N AU - Kato N AD - Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba. FAU - Shioji, K AU - Shioji K AD - Department of Internal medicine, Niigata Cancer Center Hospital, Niigata. FAU - Shimizu, K AU - Shimizu K AD - Department of Gastroenterology, Tokyo Women's Medical University, Tokyo. FAU - Nakagohri, T AU - Nakagohri T AD - Gastroenterological Surgery, Tokai University School of Medicine, Isehara. FAU - Kamata, K AU - Kamata K AD - Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka. FAU - Ishii, H AU - Ishii H AD - Clinical Research Center, Chiba Cancer Center, Chiba, Japan. FAU - Furuse, J AU - Furuse J AD - Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo. CN - members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG) LA - eng SI - UMIN-CTR/UMIN000010667 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Drug Combinations) RN - 0W860991D6 (Deoxycytidine) RN - 150863-82-4 (S 1 (combination)) RN - 1548R74NSZ (Tegafur) RN - 5VT6420TIG (Oxonic Acid) RN - Q20Q21Q62J (Cisplatin) RN - 0 (Gemcitabine) SB - IM CIN - Ann Oncol. 2019 Dec 1;30(12):1851-1852. PMID: 31638143 MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Biliary Tract Neoplasms/*drug therapy/epidemiology/pathology MH - Cisplatin/*administration & dosage/adverse effects MH - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives MH - Disease-Free Survival MH - Drug Combinations MH - Female MH - Humans MH - Japan/epidemiology MH - Male MH - Middle Aged MH - Nausea/chemically induced/pathology MH - Oxonic Acid/administration & dosage/adverse effects MH - Tegafur/administration & dosage/adverse effects MH - Vomiting/chemically induced/pathology MH - Gemcitabine OTO - NOTNLM OT - advanced biliary tract cancer OT - first-line chemotherapy OT - gemcitabine plus S-1 OT - phase III randomized trial EDAT- 2019/10/01 06:00 MHDA- 2020/07/28 06:00 CRDT- 2019/10/01 06:00 PHST- 2019/10/01 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2019/10/01 06:00 [entrez] AID - S0923-7534(20)32557-6 [pii] AID - 10.1093/annonc/mdz402 [doi] PST - ppublish SO - Ann Oncol. 2019 Dec 1;30(12):1950-1958. doi: 10.1093/annonc/mdz402.