title: Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer.
abstract: OBJECTIVE
  To evaluate the dose-limiting toxicities (DLTs) and determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.
  
  
  METHODS
  Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine (mg/m(2)), cisplatin (mg/m(2)), and S-1 (mg/m(2) per day) were as follows: level -1, 800/20/60; level 0, 800/25/60; level 1, 1000/25/60; and level 2, 1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15, and S-1 was administered orally twice daily on days 1 to 7 and days 15 to 21, every 4 wk.
  
  
  RESULTS
  Twelve patients were enrolled, and level 0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs (grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1. We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase II study.
  
  
  CONCLUSIONS
  The RD was defined as gemcitabine 1000 mg/m(2) (days 1, 15), cisplatin 25 mg/m(2) (days 1, 15), and S-1 80 mg/m(2) per day (days 1-7, 15-21), every 4 weeks. A phase II study is planned to evaluate the effectiveness of combination chemotherapy with gemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kida
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Miyazawa
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Iwai
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okuwaki
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Miyoko
authors.initials: M
authors.lastname: Takezawa
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imaizumi
authors.affiliation: Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Advanced biliary tract cancer; Cisplatin, S-1; Gemcitabine