title: Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease.
abstract: BACKGROUND
  The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment.
  
  
  METHODS
  Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed.
  
  
  RESULTS
  The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28-61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08-1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08-11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities.
  
  
  CONCLUSIONS
  The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Room 211B, 2/F New Clinical Building, 102 Pokfulam Road, Hong Kong, China. the@netvigator.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Yau
authors.forename: Hilda
authors.initials: H
authors.lastname: Wong
authors.forename: Pierre
authors.initials: P
authors.lastname: Chan
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: R
authors.initials: R
authors.lastname: Pang
authors.forename: T T
authors.initials: TT
authors.lastname: Cheung
authors.forename: S T
authors.initials: ST
authors.lastname: Fan
authors.forename: Ronnie T
authors.initials: RT
authors.lastname: Poon
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010671:Phenylurea Compounds; D011799:Quinazolines; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride