title: Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) and ligand expression is frequently seen in hepatocellular carcinoma (HCC). A phase 2 study was performed with cetuximab, a chimeric monoclonal antibody that binds specifically to EGFR, in patients with advanced HCC.
  
  
  METHODS
  Eligibility criteria included unresectable or metastatic measurable HCC, an Eastern Cooperative Oncology Group performance status <or=2, Cancer of the Liver Italian Program (CLIP) score <or=3, and adequate organ functions. The initial dose of cetuximab was 400 mg/m(2) given intravenously followed by weekly intravenous infusions at 250 mg/m(2). Each cycle was defined as 6 consecutive weekly treatments. EGFR expression was assayed by immunohistochemistry and trough serum concentrations of cetuximab were determined during the first cycle.
  
  
  RESULTS
  Thirty patients were enrolled and assessable for efficacy and toxicity. No responses were seen. Five patients had stable disease (median time, 4.2 months; range, 2.8-4.2 months). The median overall survival was 9.6 months (95% confidence interval [CI], 4.3-12.1 months) and the median progression-free survival (PFS) was 1.4 months (95% CI, 1.2-2.6 months). The treatment was generally well tolerated. No treatment-related grade 4-5 toxicities occurred. Grade 3 (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [version 3.0]) aspartate aminotransferase, hypomagnesemia, and fever without neutropenia were noted in 1 patient (3.3%) each. On Week 6 of Cycle 1, arithmetic mean serum cetuximab concentrations for patients with Child-Turcotte-Pugh (CTP) A and CTP B disease were 47.6 mcg/mL and 66.9 mcg/mL, respectively.
  
  
  CONCLUSIONS
  Although cetuximab could be safely administered with tolerable toxicity profiles, it demonstrated no antitumor activity in HCC in this phase 2 study. Cetuximab trough concentrations were not notably altered in patients with mild to moderate hepatic dysfunction.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. azhu@partners.org
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Keith
authors.initials: K
authors.lastname: Stuart
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Donald P
authors.initials: DP
authors.lastname: Reitberg
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Peter C
authors.initials: PC
authors.lastname: Enzinger
authors.forename: Pankaj
authors.initials: P
authors.lastname: Bhargava
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: Kerry
authors.initials: K
authors.lastname: Horgan
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000068818:Cetuximab; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab