Targeting epidermal growth factor receptor in head and neck cancer: lessons learned from cetuximab.

As early detection strategies have not been successful, most patients with head and neck cancer (HNC) present with advanced (stages III and IV) disease. Oral cavity tumors are treated primarily with surgical resection and advanced tumors of the pharynx and larynx are generally treated with combined modality therapy (chemoradiation). The major advances in the management of HNC have evolved from the integration of targeted therapeutics into treatment regimens. Presently, the most important target for new therapeutic strategies in HNC is the epidermal growth factor receptor (EGFR) and so far only cetuximab, a monoclonal antibody targeting EGFR, has been approved by the United States Food and Drug Administration in the HNC population as a radiation-sensitizing agent for patients undergoing primary radiation-based treatment and for patients with recurrent or metastatic disease. Other receptor and non-receptor kinase targeting strategies are under active clinical investigation as well. The increasing number of molecular targeting strategies in clinical development underscores the need to identify which HNC patients will respond to specific therapies. This article focuses on the current preclinical and clinical evidence of monoclonal antibodies targeting EGFR in HNC. We will first review the mechanisms of action of cetuximab, its clinical trials and side-effect profiles, and its present clinical application. Then, the current development status of other molecular antibodies and two molecular inhibitors, gefitinib and erlotinib, will be examined. Finally, by focusing on cetuximab, the current issues in EGFR targeting will be reviewed and we propose future directions of EGFR targeting. We hope that this review will provide further insight into the future directions of targeted therapy in the management of advanced HNC.