Second-line chemotherapy in biliary tract cancer: Outcome and prognostic factors

Liver Int. 2019 May;39(5):914-923. doi: 10.1111/liv.14063. Epub 2019 Mar 18.

Abstract

Background & aims: The prognosis of biliary tract cancer (BTC) is poor. Standard treatment for advanced BTC is a chemotherapy (CT) with gemcitabine and cisplatin. Phase III evidence for a second-line (2L) CT is lacking. We aimed to investigate the feasibility of a 2L CT, to estimate the outcome and to identify prognostic markers.

Methods: Patients of our institution with advanced BTC between 2000 and 2015 receiving CT were included. Data were analysed in univariate and multivariate analysis.

Results: Three-hundred and fifteen and 144 patients (45.7%) received first-line (1L) and 2L CT respectively. The OS of patients receiving 2L CT was 16.67 and 9.9 months from the beginning of 1L and 2L CT respectively. The overall response rate and the disease control rate after 3 months were 9.7% and 33.6% respectively. Adverse events of grade 3 or more were observed in 26.1%. One patient died of gemcitabine-related haemolytic uraemic syndrome. Age of more than 70 years was not associated with a poor outcome. In multivariate analysis, CEA levels of >3 µg/L (P = 0.004, hazard ratio [HR] 1.89, 95% CI 1.22, 2.91), cholinesterase (CHE) levels of <5 kU/L (P = 0.001, HR 2.11, 95% CI 1.34, 3.31) and leukocytosis (P = 0.001, HR 2.90, 95% CI 1.51, 5.56) were associated with poor survival.

Conclusions: Despite a relevant toxicity, our data suggest that 2L CT may be feasible in fit BTC patients. CEA elevation, leukocytosis and low CHE levels are unfavourable prognostic markers. Results from prospective randomized trials are urgently awaited.

Keywords: biliary tract cancer; chemotherapy; cholangiocarcinoma; second line.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / mortality
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / mortality
  • Cisplatin / administration & dosage
  • Clinical Trials as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gallbladder Neoplasms / drug therapy*
  • Gallbladder Neoplasms / mortality
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Cisplatin
  • Gemcitabine