PMID- 35900311
OWN - NLM
STAT- MEDLINE
DCOM- 20230116
LR  - 20230413
IS  - 1868-6982 (Electronic)
IS  - 1868-6974 (Print)
IS  - 1868-6974 (Linking)
VI  - 30
IP  - 1
DP  - 2023 Jan
TI  - Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, 
      cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA).
PG  - 102-110
LID - 10.1002/jhbp.1219 [doi]
AB  - BACKGROUND: Gemcitabine/cisplatin (GC) combination therapy has been the standard 
      palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No 
      randomized clinical trials have been able to demonstrate the survival benefit 
      over GC during the past decade. In our previous phase II trial, adding S-1 to GC 
      (GCS) showed promising efficacy and we aimed to determine whether GCS could 
      improve overall survival compared with GC for patients with advanced BTC. 
      METHODS: We performed a mulitcenter, randomized phase III trial across 39 
      centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC 
      arm. The GCS regimen comprised gemcitabine (1000 mg/m(2) ) and cisplatin 
      (25 mg/m(2) ) infusion on day 1 and 80 mg/m(2) of S-1 on days 1-7 every 2 weeks. 
      The primary endpoint was overall survival (OS) and the secondary endpoints were 
      progression-free survival (PFS), response rate (RR), and adverse events (AEs). 
      This study is registered with Clinical trial identification: NCT02182778. 
      RESULTS: Between July 2014 and February 2016, 246 patients were enrolled. The 
      median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 
      12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% 
      confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). 
      Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 
      95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC 
      arm. Grade 3 or worse AEs did not show significant differences between the two 
      arms. CONCLUSIONS: GCS is the first regimen which demonstrated survival benefits 
      as well as higher RR over GC in a randomized phase III trial and could be the new 
      first-line standard chemotherapy for advanced BTC. To exploit the advantage of 
      its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase 
      III trial for potentially resectable BTC.
CI  - (c) 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by 
      John Wiley & Sons Australia, Ltd on behalf of Japanese Society of 
      Hepato-Biliary-Pancreatic Surgery.
FAU - Ioka, Tatsuya
AU  - Ioka T
AUID- ORCID: 0000-0002-0197-1832
AD  - Department of Oncology Center, Yamaguchi University Hospital, Yamaguchi, Japan.
AD  - Department of Cancer Survey and Gastrointestinal Oncology, Osaka International 
      Cancer Institute, Osaka, Japan.
FAU - Kanai, Masashi
AU  - Kanai M
AD  - Department of Medical Oncology, Kyoto University Hospital, Kyoto, Japan.
FAU - Kobayashi, Shogo
AU  - Kobayashi S
AD  - Department of Gastroenterological Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Sakai, Daisuke
AU  - Sakai D
AD  - Department of Frontier Science for Cancer and Chemotherapy, Osaka University, 
      Osaka, Japan.
FAU - Eguchi, Hidetoshi
AU  - Eguchi H
AUID- ORCID: 0000-0002-2318-1129
AD  - Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
FAU - Baba, Hideo
AU  - Baba H
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Science, 
      Kumamoto University, Kumamoto, Japan.
FAU - Seo, Satoru
AU  - Seo S
AUID- ORCID: 0000-0001-9539-8098
AD  - Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 
      Japan.
FAU - Taketomi, Akinobu
AU  - Taketomi A
AD  - Department of Gastroenterological Surgery I, Hokkaido University Graduate School 
      of Medicine, Hokkaido, Japan.
FAU - Takayama, Tadatoshi
AU  - Takayama T
AD  - Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, 
      Japan.
FAU - Yamaue, Hiroki
AU  - Yamaue H
AD  - Second Department of Surgery, School of Medicine, Wakayama Medical University, 
      Wakayama, Japan.
FAU - Takahashi, Masahiro
AU  - Takahashi M
AD  - Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan.
FAU - Sho, Masayuki
AU  - Sho M
AUID- ORCID: 0000-0002-6208-7661
AD  - Department of Surgery, Nara Medical University, Nara, Japan.
FAU - Kamei, Keiko
AU  - Kamei K
AD  - Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan.
FAU - Fujimoto, Jiro
AU  - Fujimoto J
AD  - Department of Gastroenterological Surgery, Hyogo College of Medicine, Hyogo, 
      Japan.
FAU - Toyoda, Masanori
AU  - Toyoda M
AD  - Department of Medical Oncology/Hematology, Kobe University Hospital and Graduate 
      School of Medicine, Hyogo, Japan.
FAU - Shimizu, Junzo
AU  - Shimizu J
AD  - Department of Surgery, Toyonaka Municipal Hospital, Osaka, Japan.
FAU - Goto, Takuma
AU  - Goto T
AD  - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, 
      Asahikawa Medical University, Hokkaido, Japan.
FAU - Shindo, Yoshitaro
AU  - Shindo Y
AUID- ORCID: 0000-0001-7419-5638
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Yamaguchi, Japan.
FAU - Yoshimura, Kenichi
AU  - Yoshimura K
AD  - Medical Center for Clinical and Translational Research, Hiroshima University 
      Hospital, Hiroshima, Japan.
FAU - Hatano, Etsuro
AU  - Hatano E
AD  - Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 
      Japan.
FAU - Nagano, Hiroaki
AU  - Nagano H
AD  - Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi 
      University Graduate School of Medicine, Yamaguchi, Japan.
CN  - Kansai Hepatobiliary Oncology Group (KHBO)
LA  - eng
SI  - ClinicalTrials.gov/NCT02182778
GR  - Taiho Pharmaceutical/
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220809
PL  - Japan
TA  - J Hepatobiliary Pancreat Sci
JT  - Journal of hepato-biliary-pancreatic sciences
JID - 101528587
RN  - 0 (Gemcitabine)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0W860991D6 (Deoxycytidine)
SB  - IM
MH  - Humans
MH  - Gemcitabine
MH  - Cisplatin
MH  - *Biliary Tract Neoplasms/drug therapy
MH  - Deoxycytidine/therapeutic use
MH  - *Bile Duct Neoplasms/drug therapy/chemically induced
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Treatment Outcome
PMC - PMC10086809
OTO - NOTNLM
OT  - S-1
OT  - biliary tract cancer
OT  - cisplatin
OT  - gemcitabine
COIS- TI has received personal fees from Incyte, Chugai, Yakult Honsha, Taiho 
      Pharmaceutical, Ono Pharm, Servier, Daiichi Sankyo, Nihon Zouki, Eli-Lilly, 
      Otsuka, Novartis, AstraZeneca and Abbott. MK has received personal fees from 
      Chugai. MT has received personal fees from Ono. KY has received personal fees 
      from Ohara, Nihon-Shinyaku, Sysmex, Chugai Pharma, Eli-Lilly, Astra Zeneca, 
      Otsuka, Novartis, Eisai, Nihon-Kayaku, Boehringer Ingelheim, Taiho and Pfizer. EH 
      has received personal fees from Eli-Lilly and Taiho. The other authors declare 
      that they have no competing interest.
EDAT- 2022/07/29 06:00
MHDA- 2023/01/17 06:00
PMCR- 2023/04/11
CRDT- 2022/07/28 10:52
PHST- 2022/06/22 00:00 [revised]
PHST- 2022/03/23 00:00 [received]
PHST- 2022/07/18 00:00 [accepted]
PHST- 2022/07/29 06:00 [pubmed]
PHST- 2023/01/17 06:00 [medline]
PHST- 2022/07/28 10:52 [entrez]
PHST- 2023/04/11 00:00 [pmc-release]
AID - JHBP1219 [pii]
AID - 10.1002/jhbp.1219 [doi]
PST - ppublish
SO  - J Hepatobiliary Pancreat Sci. 2023 Jan;30(1):102-110. doi: 10.1002/jhbp.1219. 
      Epub 2022 Aug 9.