title: A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas.
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.
  
  
  CONCLUSIONS
  The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Capanu
authors.forename: E M
authors.initials: EM
authors.lastname: O'Reilly
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: J F
authors.initials: JF
authors.lastname: Chou
authors.forename: J
authors.initials: J
authors.lastname: Shia
authors.forename: S S
authors.initials: SS
authors.lastname: Katz
authors.forename: B
authors.initials: B
authors.lastname: Gansukh
authors.forename: D
authors.initials: D
authors.lastname: Reidy-Lagunes
authors.forename: N H
authors.initials: NH
authors.lastname: Segal
authors.forename: K H
authors.initials: KH
authors.lastname: Yu
authors.forename: K-Y
authors.initials: KY
authors.lastname: Chung
authors.forename: L B
authors.initials: LB
authors.lastname: Saltz
authors.forename: G K
authors.initials: GK
authors.lastname: Abou-Alfa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D010671:Phenylurea Compounds; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin; D000093542:Gemcitabine
references.citation: J Clin Oncol. 2006 Mar 1;24(7):1152-60
references.pmid: 16505435
references.citation: Br J Cancer. 2006 Oct 9;95(7):848-52
references.pmid: 16969352
references.citation: Br J Cancer. 2008 Jan 29;98(2):418-25
references.pmid: 18087285
references.citation: PLoS One. 2010 Dec 29;5(12):e15588
references.pmid: 21206909
references.citation: Clin Colorectal Cancer. 2005 Sep;5(3):188-96
references.pmid: 16197622
references.citation: Cancer Res. 2003 Mar 1;63(5):1083-92
references.pmid: 12615726
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Cancer Res. 2004 Oct 1;64(19):7099-109
references.pmid: 15466206
references.citation: N Engl J Med. 2010 Apr 8;362(14):1273-81
references.pmid: 20375404
references.citation: Br J Cancer. 2008 Jan 29;98(2):309-15
references.pmid: 18182984
references.citation: Clin Cancer Res. 2006 Jan 1;12(1):144-51
references.pmid: 16397036
references.citation: Invest New Drugs. 2012 Aug;30(4):1646-51
references.pmid: 21748296
references.citation: Cancer Res. 2002 Nov 15;62(22):6500-5
references.pmid: 12438243
references.citation: Br J Cancer. 2009 Aug 18;101(4):621-7
references.pmid: 19672264
references.citation: Gut. 2003 May;52(5):706-12
references.pmid: 12692057