An open-label, phase I study of cetuximab to assess the safety, efficacy and pharmacokinetics (PK) of different cetuximab regimens in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC).

3632 Background: Cetuximab (Erbitux) is an IgG1 monoclonal antibody that targets the human EGFR. Cetuximab has been shown to be active in patients with advanced CRC refractory to irinotecan-based chemotherapy, both as a single agent and when combined with irinotecan. Methods: The purpose of this study was to characterize the safety, efficacy and PK of cetuximab following the approved regimen (Group A) (initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2) and two exploratory regimens (weekly doses of 250 mg/m2 (Group B) or 350 mg/m2 (Group C) respectively not preceded by a higher initial dose) in patients with EGFR-expressing, refractory mCRC. Skin biopsies were taken to correlate biological activity with the different schedules. Results: 49 patients were enrolled on a sequential basis and evaluated for safety and efficacy, and 45 patients were evaluated for PK. PK parameters for Group A were in good agreement with historical data. Dose-related, predictable increases in Cmax and AUCτ were obse...