A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas

Br J Cancer. 2013 Aug 20;109(4):915-9. doi: 10.1038/bjc.2013.432. Epub 2013 Jul 30.

Abstract

Background: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy.

Methods: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome.

Results: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes.

Conclusion: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Extrahepatic / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / pathology
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Gallbladder Neoplasms / drug therapy
  • Gallbladder Neoplasms / pathology
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds / administration & dosage
  • Sorafenib
  • Treatment Outcome

Substances

  • Phenylurea Compounds
  • Deoxycytidine
  • Niacinamide
  • Sorafenib
  • Cisplatin
  • Gemcitabine