title: Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Lamarca
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Benafif
authors.affiliation: Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Ross
authors.affiliation: UCL Cancer Institute, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Bridgewater
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Institute of Cancer Studies, University of Manchester, Manchester Academic Health Science Centre (MAHSC), United Kingdom. Electronic address: juan.valle@manchester.ac.uk.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007565:Jaundice / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015607:Stents; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D015415:Biomarkers; D003841:Deoxycytidine; D002945:Cisplatin; D001663:Bilirubin; D000093542:Gemcitabine
keywords: Advanced biliary tract cancer; Bilirubin; Chemotherapy; Cisplatin; Gemcitabine; Jaundice