Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer

J Hepatobiliary Pancreat Sci. 2015 Sep;22(9):669-74. doi: 10.1002/jhbp.255. Epub 2015 Apr 15.

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.

Keywords: Biliary tract cancer; Cholangiocarcinoma; Cisplatin; Gallbladder carcinoma; Gemcitabine; S-1.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Biliary Tract Neoplasms / diagnosis
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / mortality
  • Cisplatin / administration & dosage*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Staging*
  • Oxonic Acid / administration & dosage*
  • Retrospective Studies
  • Survival Rate / trends
  • Tegafur / administration & dosage*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Cisplatin
  • Gemcitabine