Abstract 3508: High antitumor activity of cetuximab combined with taxotere-cisplatin-flourouracil (TPF) association on an orthotopic head and neck cancer model

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background : Cetuximab (cetux), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard of care in advanced head and neck (HN) cancer when combined with irradiation or cisplatin. The TPF association including taxotere (T), cisplatin (P) and fluorouracil (F) has become a chemotherapy of reference in the management of HN tumors. The aim of the study was to evaluate the antitumor activity of the association of cetux with TPF. In addition the potential benefit to add bevacizumab (beva), an anti-VEGF monoclonal antibody, was also examined. Methods : investigations were performed on CAL33 human head and neck cancer cell line (high content of EGFR) injected as an orthotopic xenograft into the mouth floor of nude mice. The anti-tumor efficacy of cetux 2,5 mg/kg, beva 20 mg/kg and of TPF at the MTD (T : 20 mg/kg, P : 6 mg/kg, and F : 17mg/kg) administered alone or in combination at day 3 and 10 after tumor cell injection was assessed at day 12 (animal sacrifice for ethical reasons, 10 animals per treatment group). Tumor volume, tumor histology, tumor cell proliferation (Ki67 by immunohistochemistry) and apoptosis (Bcl2 by immunohistochemistry) were examined. Statistical analyses were performed according to non-parametric methods. Results : As compared to controls, TPF-cetux and TPF-cetux-beva had a significant impact on tumor volume and histological response. The highest efficacy was observed with the combination TPF-cetux. The effects of the association TPF-cetux-beva were not significantly different than those observed with TPF-cetux. Data were corroborated by a diminution in Ki67 labelling and Bcl2 expression. Conclusion : the association of cetux with TPF could be an interesting clinical option to evaluate in advanced HN cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3508. doi:10.1158/1538-7445.AM2011-3508