Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113

Sci Rep. 2021 Jun 18;11(1):12885. doi: 10.1038/s41598-021-92166-3.


JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504-0.937) in the low CCr group. Although the total number of incidences of all Grade 3-4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / complications
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / pathology*
  • Biomarkers
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Management
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases / diagnosis
  • Kidney Diseases / etiology
  • Kidney Function Tests
  • Male
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Treatment Outcome


  • Biomarkers
  • Deoxycytidine
  • gemcitabine