Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma

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 <= 2, Cancer of the Liver Italian Program (CLIP) score <= 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 amino transferase, hypomagnesemia, and fever without neutropenia were noted in I 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.