New approaches to enhance chemotherapy in SCCHN.

Chemotherapy is the standard approach to the treatment of patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) and is also now a common component of treatment for patients with locoregionally advanced, non-metastatic disease. Cisplatin has for many years been the agent of choice, alone or in combination with other agents, particularly 5-FU. The advent of the taxanes, which demonstrate good non-clinical activity against SCCHN, spawned a series of investigations aimed at integrating these agents into treatment regimens. Molecular targeted agents, which do not demonstrate overlapping toxicities with commonly used chemotherapy agents for SCCHN, represent a promising avenue of investigation. The epidermal growth factor receptor (EGFR) is expressed both widely and at high levels in SCCHN and is associated with poor prognosis. The EGFR-directed monoclonal antibody (MAb) cetuximab (Erbitux) in combination with chemotherapy has shown some activity in the treatment of recurrent/metastatic disease both as first-line therapy and following cisplatin failure, and preliminary results suggest single-agent activity in platinum-resistant disease. Promising activity has also been observed with a number of other EGFR inhibitors, both MAbs and tyrosine kinase inhibitors.