Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease

Eur J Cancer. 2015 Sep;51(13):1694-703. doi: 10.1016/j.ejca.2015.05.018. Epub 2015 Jun 8.

Abstract

Introduction: The advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1(st)-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾ 1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin.

Methods: Patients with ABC, receiving CisGem with a baseline bilirubin of ⩾ 1.5 × ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected.

Results: Thirty-three patients of 545 screened; median age 59 years, range 23-79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55 μmol/L (range 32-286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9 months (95% confidence interval (CI): 4.4-9.0) and median overall survival (OS) 9.5 months (95% CI: 5.7-12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6 months; p = 0.1633 and 9.8 versus 4.4 months, hazard ratio (HR) 0.74; p = 0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9 months, HR 0.49; p = 0.08 and 15.2 versus 5.4 months, HR 0.12 p < 0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS).

Conclusion: For PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin.

Keywords: Advanced biliary tract cancer; Bilirubin; Chemotherapy; Cisplatin; Gemcitabine; Jaundice.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / complications
  • Biliary Tract Neoplasms / diagnosis
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / mortality
  • Bilirubin / blood
  • Biomarkers / blood
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Jaundice / diagnosis
  • Jaundice / etiology
  • Jaundice / therapy*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Palliative Care
  • Patient Selection
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Stents*
  • Time Factors
  • Treatment Outcome
  • United Kingdom
  • Young Adult

Substances

  • Biomarkers
  • Deoxycytidine
  • gemcitabine
  • Cisplatin
  • Bilirubin