title: Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC).
  
  
  METHODS
  Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point.
  
  
  RESULTS
  Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child's A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea.
  
  
  CONCLUSIONS
  In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients.
authors.affiliation: Karmanos Cancer Institute, Detroit, Michigan 48201, USA. philipp@karmanos.org
authors.forename: Philip A
authors.initials: PA
authors.lastname: Philip
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Holen
authors.forename: Donald W
authors.initials: DW
authors.lastname: Northfelt
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride