Single-institution experience with gemcitabine-cisplatin combination therapy as a second-line treatment for patients with unresectable biliary tract cancer after failure of gemcitabine-S-1 combination therapy: a prospective feasibility study

Cancer Chemother Pharmacol. 2018 May;81(5):949-955. doi: 10.1007/s00280-018-3566-z. Epub 2018 Mar 28.

Abstract

Background: NCCN and Japanese clinical guidelines for the treatment of biliary tract cancer (BTC) addressed gemcitabine-cisplatin combination (GC) as first-line chemotherapy for patients with advanced BTC ineligible for surgery in 2013. However, gemcitabine-S1 combination therapy (GS) has been widely used as first-line treatment in Japan because Japanese social insurance coverage of S-1 for BTC was approved prior to that of cisplatin.

Aim: To elucidate the efficacy and tolerability of GC as second-line chemotherapy for patients with unresectable BTC after failure of GS.

Patients and methods: Between September 2008 and August 2011, patients with unresectable BTC who provided informed consent and received GC comprising gemcitabine at 1000 mg/m2 and cisplatin at 20 mg/m2 given on days 1 and 8 in a 3-week cycle after failure of GS were included in the present study. Clinical data from these patients were collected prospectively. Primary endpoints were overall survival and time to progression (TTP). Secondary endpoints were response and tolerability.

Results: Twenty-seven patients were analyzed. Median survival time (MST) and TTP from the beginning of second-line treatment were 6.5 and 3.3 months, respectively, whereas MST from the commencement of first-line therapy was 12.06 months. One patient showed partial response, 16 had stable disease and 10 experienced disease progression. As a result, disease control rate was 63.0%. In total, 119 courses (median, 4; range, 1-15) were administered. Discontinuation of GC due to drug toxicities was not observed.

Conclusion: Although some issues remain to be clarified, mainly due to the small sample size, this single-institution experience with GC as second-line treatment after failure of GS showed acceptable outcomes and good tolerability.

Keywords: Biliary tract cancer; Cisplatin; Gemcitabine; Refractory; S-1.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / pathology
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Combinations
  • Feasibility Studies
  • Female
  • Gemcitabine
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Oxonic Acid / pharmacology*
  • Oxonic Acid / therapeutic use
  • Progression-Free Survival
  • Prospective Studies
  • Survival Analysis
  • Tegafur / pharmacology*
  • Tegafur / therapeutic use
  • Time Factors
  • Treatment Failure

Substances

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

Associated data

  • JPRN/UMIN000007571