Randomized phase II study of gemcitabine plus S-1 versus S-1 in advanced biliary tract cancer: a Japan Clinical Oncology Group trial (JCOG 0805)

Cancer Sci. 2013 Sep;104(9):1211-6. doi: 10.1111/cas.12218. Epub 2013 Jul 25.

Abstract

The oral fluoropyrimidine, S-1, combined with or without gemcitabine is considered to be a promising agent for treating advanced biliary tract cancer; gemcitabine plus cisplatin is the current standard regimen. This randomized phase II trial was designed to evaluate the safety and efficacy of two regimens: gemcitabine plus S-1 (GS) (gemcitabine: 1000 mg/m(2) , day 1 and day 8; S-1: 60 mg/m(2) , twice daily on days 1-14, repeated every 3 weeks); and S-1 (80 mg/m(2) , days 1-28, given orally twice daily for 4 weeks, followed by a 2-week rest, repeated every 6 weeks). The regimen with a higher 1-year survival would be selected for a subsequent phase III trial. Between February 2009 and April 2010, 101 patients were randomized. For the GS (n = 51) and S-1 (n = 50) arms, the 1-year survival was 52.9% (95% confidence interval, 38.5-65.5) and 40.0% (95% confidence interval, 26.5-53.1), and the median survival times were 12.5 and 9.0 months, respectively. Grade 3/4 hematological toxicities were more frequent in the GS arm (leucocytes 29.4%, neutrophils 60.8%, hemoglobin 11.8%, platelets 11.8%) than in the S-1 arm (leucocytes 2.0%, neutrophils 4.0%, hemoglobin 4.0%, platelets 4.0%). Although two treatment-related deaths occurred in the GS arm, all other grade 3/4 non-hematological toxicities were reversible. In conclusion, GS was considered to be more promising and was selected as the test regimen for a subsequent phase III trial comparing GS with gemcitabine plus cisplatin combination therapy. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001685 (http://www.umin.ac.jp/ctr/index.htm).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Drug Combinations
  • Female
  • Gemcitabine
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Tegafur / administration & dosage
  • Tegafur / adverse effects

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Gemcitabine