Enhanced Antitumor Activity of Anti-epidermal Growth Factor Receptor Monoclonal Antibody IMC-C225 in Combination with Irinotecan (CPT-11) against Human Colorectal Tumor Xenografts

摘要: Colon carcinomas frequently express the epidermal growth factor receptor (EGFR), and this expression correlates with more aggressive disease poor prognosis. Previous studies have shown that EGFR blockade by monoclonal antibody IMC-C225 can inhibit of human colon carcinoma tumor cells in vitro xenografts these tumors athymic mice. In report, we studied vivo activity combined topoisomerase I inhibitor irinotecan (CPT-11) using two models colorectal nude was tested at a dose 1 or 0.5 mg administered q3d. CPT-11 100 mg/kg/week maximum tolerated 150 mg/kg/week. Treatment combination (1 mg) (100 mg/kg) significantly inhibited established DLD-1 HT-29 compared either monotherapy (P < 0.05). Combination therapy MTD (150 resulted regression rate 60% tumors, respectively. refractory model, treatment whereas agent alone did not control growth. Histological examination treated showed extensive necrosis, decreased cell proliferation, increased apoptosis, marked decrease vasculature. These results suggest inhibitors may be an effective against chemorefractory tumors.