Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial

Br J Cancer. 2010 Jan 5;102(1):68-72. doi: 10.1038/sj.bjc.6605458. Epub 2009 Nov 24.

Abstract

Background: Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma.

Methods: We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks.

Results: A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P=0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients.

Conclusions: Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzenesulfonates / adverse effects
  • Benzenesulfonates / therapeutic use*
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / pathology
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / pathology
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / pathology
  • Disease-Free Survival
  • Drug Eruptions / etiology
  • Fatigue / chemically induced
  • Female
  • Gallbladder Neoplasms / drug therapy
  • Gallbladder Neoplasms / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Salvage Therapy
  • Sorafenib

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Sorafenib