title: Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer.
abstract: BACKGROUND
  To develop a triplet regimen containing gemcitabine, cisplatin, and S-1 (GPS), we assessed the recommended dose for patients with untreated advanced biliary tract cancer in this phase I study.
  
  
  METHODS
  Dose-limiting toxicities (DLTs) were evaluated for the following two dose levels: gemcitabine (1000 mg/m(2) for level 1 and 1200 mg/m(2) for level 2 on day 1), cisplatin (30 mg/m(2) fixed dose on day 1), and S-1 (40-60 mg/day fixed dose twice a day for 7 days), every 2 weeks until progression. DLTs for each level were evaluated in six or more patients during the first two cycles.
  
  
  RESULTS
  A total of 18 patients were enrolled and 16 patients were evaluated. DLTs at level 1 were observed in two of 10 patients. At level 2, a DLT was observed in one of six patients. The main grade 3 or 4 treatment-related adverse events were neutropenia and leukopenia, and a few non-hematological toxicities were observed. Among 14 patients with measurable lesions, the best response rate was 50%.
  
  
  CONCLUSIONS
  GPS with a relative dose intensity corresponding to 90% of the standard gemcitabine plus cisplatin regimen could be administered safely, and showed preliminary antitumor activity. Survival benefits will be studied subsequently.
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Toshikazu
authors: T
authors: Moriwaki
authors: Department of Gastroenterology, Mito Medical Center, National Hospital Organization, Ibaraki, Japan.
authors: Hiroyasu
authors: H
authors: Ishida
authors: Division of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Ibaraki, Japan.
authors: Masahiro
authors: M
authors: Araki
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Shinji
authors: S
authors: Endo
authors: Department of Gastroenterology, Mito Medical Center, National Hospital Organization, Ibaraki, Japan.
authors: Shigemasa
authors: S
authors: Yoshida
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Mariko
authors: M
authors: Kobayashi
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Yukako
authors: Y
authors: Hamano
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Akinori
authors: A
authors: Sugaya
authors: Department of Gastroenterology, Mito Medical Center, National Hospital Organization, Ibaraki, Japan.
authors: Masahiro
authors: M
authors: Shimoyamada
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Naoyuki
authors: N
authors: Hasegawa
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Mamiko
authors: M
authors: Imanishi
authors: Department of Gastroenterology, Mito Medical Center, National Hospital Organization, Ibaraki, Japan.
authors: Yuka
authors: Y
authors: Ito
authors: Department of Gastroenterology, Mito Medical Center, National Hospital Organization, Ibaraki, Japan.
authors: Daiki
authors: D
authors: Sato
authors: Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki, 305-8575, Japan.
authors: Ichinosuke
authors: I
authors: Hyodo
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001661:Biliary Tract Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D005641:Tegafur / Q000008:administration & dosage*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Biliary tract cancer; Cholangiocarcinoma; Cisplatin; Gallbladder carcinoma; Gemcitabine; S-1