title: Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model.
abstract: BACKGROUND
  Cetuximab (Cet), 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 combining docetaxel (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 anti-tumor activity of the association of Cet with TPF. In addition, the potential benefit from adding bevacizumab (Bev), an anti-VEGF monoclonal antibody, was 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 Cet (2.5 mg/kg), Bev (20 mg/kg) and of TPF (at the MTD: T 20 mg/kg, P 6 mg/kg, F 17 mg/kg), administered alone or in combination on day 3 and day 10 after tumor cell injection, was assessed on day 12 (animal sacrifice for ethical reasons, 10 animals per treatment group). Tumor volume, tumor histology, tumor cell proliferation (Ki67, immunochemistry) and apoptosis (Bcl2, immunochemistry) were examined.
  
  
  RESULTS
  As compared to controls, TPF-Cet and TPF-Cet-Bev had a significant impact on tumor volume and histological response. The highest efficacy was observed with the TPF-Cet combination. The effects of the TPF-Cet-Bev association were not significantly different from those observed with TPF-Cet. Data were corroborated by a diminution in Ki67 labeling and Bcl2 expression.
  
  
  CONCLUSIONS
  The association of Cet with TPF can be considered a beneficial clinical option in advanced HN cancer patients.
authors.affiliation: Surgery Department, Centre Antoine Lacassagne, 33 Av. de Valombrose, 06189 Nice Cedex 2, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bozec
authors.forename: Anne
authors.initials: A
authors.lastname: Sudaka
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Brunstein
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Fischel
authors.forename: Gérard
authors.initials: G
authors.lastname: Milano
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004359:Drug Therapy, Combination / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil