title: S0941: a phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma.
abstract: BACKGROUND
  Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers.
  
  
  METHODS
  Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively.
  
  
  RESULTS
  Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash.
  
  
  CONCLUSIONS
  Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease.
authors.affiliation: Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 3459, Los Angeles, CA, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: El-Khoueiry
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rankin
authors.affiliation: Departments of Medicine and Surgery, Columbia University, New York, NY, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Siegel
authors.affiliation: Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 3459, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: Division of Hematology and Oncology, University of California-Davis, Sacramento, CA, USA.
authors.forename: I-Y
authors.initials: IY
authors.lastname: Gong
authors.affiliation: Division of Hematology/Oncology, Stritch School of Medicine, Loyola University, Maywood, IL, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Micetich
authors.affiliation: Department of Internal Medicine, Hematology Oncology Section, MD Anderson Cancer Center Orlando, Orlando, FL, USA.
authors.forename: O R
authors.initials: OR
authors.lastname: Kayaleh
authors.affiliation: Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 3459, Los Angeles, CA, USA.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
authors.affiliation: Department of Medicine, Knight Cancer Institute of the Oregon Health & Science University, Portland, OR, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors