title: A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002).
abstract: OBJECTIVE
  Gemcitabine/cisplatin combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). We aimed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC.
  
  
  METHODS
  Patients with histologically or cytologically confirmed unresectable or recurrent BTC were eligible for inclusion. The primary end point was overall survival. Based on the results of our preceding phase I study, gemcitabine and cisplatin were administered intravenously at doses of 1,000 or 25 mg/m(2), respectively, on day 1, and oral S-1 was administered daily at a dose of 80 mg/m(2) on days 1-7 every 2 weeks. This study was registered with ClinicalTrials.gov (NCT01284413) and the UMIN Clinical Trials Registry (ID 000004468).
  
  
  RESULTS
  Fifty patients enrolled between October 2011 and August 2012 were evaluated. After a median follow-up of 15.1 months (range 2.4-24.4 months), the median overall survival time was 16.2 months [95% confidence interval (CI) 10.2-22.2 months], and the one-year overall survival rate was 59.9% (95% CI 46.2-73.5%). The grade 3-4 hematological toxicities were as follows: neutropenia (32%), anemia (32%), thrombocytopenia (10%), and febrile neutropenia (4%). The common grade 3-4 non-hematological toxicities were biliary tract infection (14%), anorexia/nausea (10%), and fatigue (8%).
  
  
  CONCLUSIONS
  Gemcitabine/cisplatin/S-1 combination chemotherapy offered a promising survival benefit with manageable toxicity in patients with advanced BTC. A randomized phase III trial to investigate the efficacy of this regimen compared to gemcitabine/cisplatin combination therapy in patients with advanced BTC is now underway (UMIN000014371/NCT02182778).
authors.affiliation: Department of Clinical Oncology and Pharmacogenomics, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan, kanai@kuhp.kyoto-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanai
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hatano
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Hisanori
authors.initials: H
authors.lastname: Shiomi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikuta
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Terajima
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ikoma
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kodama
authors.forename: Satoru
authors.initials: S
authors.lastname: Seo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ajiki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ioka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D000093542:Gemcitabine