Enhanced apoptosis with combination C225/radiation treatment serves as theimpetus for clinical investigation in head and neck cancers

Purpose: Epidermal growth factor receptor (EGFr) is overexpressed in a majo rity of head and neck squamous cell carcinomas, and this overexpression is associated with a poor prognosis. Therefore, EGFr has become the target of investigations aimed at disabling the receptor to determine whether this pr ocess leads to improved tumor kill with conventional treatment. Materials and Methods: C225 is an anti-EGFr monoclonal antibody that inhibi ts receptor activity by blocking the ligand binding site. A panel of human head and neck squamous cell carcinoma cell lines was used to study the comb ination of C225 and radiation. Results: It was determined that the combination of C225 (5 mug/mL) delivere d simultaneously with radiation (3 Gy) resulted in a greater decrement in c ellular proliferation than either treatment alone. This reduction in prolif eration correlated with reduced EGFr tyrosine phosphorylation and a reducti on in phosphorylated signal transducer and activator of transcription-3 (ST AT-3) protein (known to protect cells from apoptosis). Also, the decrement in proliferation correlated with increased apoptotic events, thereby indire ctly linking C225/radiation-induced regulation of STAT-3 protein to apoptos is. Conclusion: This preclinical work serves as important support for the ongoi ng clinical investigation of C225 and radiotherapy for patients with head a nd neck carcinomas. The initial results of these clinical studies have been promising. (C) 2000 by American Society of Clinical Oncology.