title: SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma.
abstract: OBJECTIVE
  Gallbladder and cholangiocarcinomas represent a heterogeneous group of malignant diseases that commonly present at an advanced stage and have limited therapeutic options. Based on the role of the Ras-Raf-Mek-Erk pathway and the VEGF axis in biliary carcinomas, we conducted a phase II study of sorafenib in patients with advanced biliary cancers.
  
  
  METHODS
  Eligible patients had no prior therapy for metastatic or unresectable disease. Sorafenib was administered at 400 mg po twice daily continuously.
  
  
  RESULTS
  The study was terminated after the first stage of accrual due to failure to meet the primary objective. A confirmed response rate of 0% (0%-11%) was observed. Thirty-nine percent of patients demonstrated stable disease (including 2 with unconfirmed PR). PFS was 3 months (95% CI: 2-4 months) and OS 9 months (95% CI: 4-12 months). The most common grade 3 and 4 toxicities included hand-foot skin reaction (13%), bilirubin elevation (13%), venous thromboembolism (10%), AST/ALT elevation (10%) and elevated alkaline phosphatase (10%).
  
  
  CONCLUSIONS
  While treatment with sorafenib did not result in objective responses, patients with biliary cancers receiving this drug had some therapeutic benefit. Additional studies with sorafenib in combination with chemotherapy or other targeted agents may be warranted.
authors: University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Suite 3459, Los Angeles, CA 90033, USA. elkhouei@usc.edu
authors: Anthony B
authors: AB
authors: El-Khoueiry
authors: Cathryn J
authors: CJ
authors: Rankin
authors: Edgar
authors: E
authors: Ben-Josef
authors: Heinz-Josef
authors: HJ
authors: Lenz
authors: Philip J
authors: PJ
authors: Gold
authors: R Darryl
authors: RD
authors: Hamilton
authors: Rangaswamy
authors: R
authors: Govindarajan
authors: Cathy
authors: C
authors: Eng
authors: Charles D
authors: CD
authors: Blanke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib