Enhanced antitumor activity with anti-epidermal growth factor receptor monoclonal antibody cetuximab in combination with carboplatin in preclinical human ovarian carcinoma models

B46 Ovarian carcinoma frequently expresses the epidermal growth factor receptor (EGFR) and this expression correlates with disease progression and patient survival. Cetuximab is an IgG1 monoclonal antibody that specifically targets the EGFR and inhibits its activation in tumor cells. In this study, we evaluated the activity of cetuximab in combination with carboplatin in two human ovarian carcinoma cell lines. Flow cytometry showed that OVCAR5 and OVCAR8 expressed significant EGFR on cell surfaces. Cetuximab treatment of ovarian cells in vitro inhibited EGF stimulated phosphorylation of the EGF receptor and cell proliferation in a dose-dependent manner. In vivo effects of Cetuximab on tumor growth were evaluated in ovarian xenograft models in athymic mice. Athymic mice with established (200 mm 3 ) OVCAR5 or OVCAR8 subcutaneous tumor xenografts were treated with cetuximab (40mg/kg; q3d), carboplatin 20mg/kg; q3d), or the combination. Treatment with cetuximab or carboplatin resulted in moderate tumor inhibition of OVCAR5 (31 and 61%, respectively) and OVCAR8 (58 and 65%, respectively) compared to saline control. Greater tumor inhibitions were observed when mice treated with the combination. The combination of cetuximab and carboplatin resulted in significantly enhanced antitumor activity in the OVCAR5 (81%) and OVCAR8 (78%) models compared to monotherapy treatment. These results suggest that the combinations of cetuximab and carboplatin may be effective approach for the treatment of ovarian carcinoma.