5048

Molecular inhibition of epidermal growth factor receptor (EGFR) function is a promising approach to cancer therapy. Cetuximab (ERBITUX®) is an IgG1 monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR) and has shown to have significant activity alone and in combination with cytotoxic agents in preclinical models of colorectal cancer. In this report, we describe the in vivo activity of cetuximab when combined with oxaliplatin therapy in HT-29 and GEO models. Treatment with combination cetuximab and oxaliplatin significantly inhibited the growth of xenograft tumors compared to single-agent therapy. In HT-29 tumors, the %T/C for combination therapy was 24% versus 59% or 57% for cetuximab or oxaliplatin alone, respectively. In the GEO tumor model, the %T/C for combination therapy was 7% compared to 24% for cetuximab monotherapy or 52% for oxaliplatin alone. This combination effect was shown to be greater-than-additive. The number of tumor regressions in the GEO model was also significantly increased with combination therapy where 8/12 animals had tumor regressions compared to 2/12 for cetuximab alone and no animals for oxaliplatin alone. Histological examination of residual tumors after combination treatment showed an increase in pyknotic nuclei and a decrease in mitotic figures; this resulted in a substantial decrease in viable tumor compartment with near elimination of neoplastic cells. The present study shows that combining cetuximab with oxaliplatin therapy warrants clinical evaluation.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]