Promising New Approaches in the Treatment of Advanced Head and Neck Cancer

Squamous cell carcinoma (SCC) of the head and neck (H&N) represents a major international health problem. The overwhelming majority of H&N cancers are strongly associated with tobacco use, and the intense global marketing of tobacco products suggests that it is unlikely there will be a decrease in H&N cancer incidence in the near future. Ongoing advances in surgical techniques continue to diminish treatment-related morbidity for patients with advanced disease. New developments in radiation and chemotherapy suggest that nonoperative treatment strategies will increasingly accomplish effective disease control, particularly with the refinement of concurrent chemoradiotherapy regimens and the use of new molecular agents which modulate H&N tumor growth. In this article, we highlight selected advances in surgery, radiation, and chemoradiation, which hold particular promise for the future of H&N cancer therapy. The evolution of surgical techniques includes the increasing use of selective neck dissection, the use of conservation techniques in the management of selected laryngeal and hypopharyngeal tumors, the use of free tissue transfer for optimal reconstruction and the increased availability of expertise in combined surgical approaches for tumors of the skull base. Altered radiation fractionation has evolved to a mature state of knowledge in recent years based primarily on clinical trials performed in patients with advanced H&N cancer. A major current challenge involves how to best interdigitate optimal radiation fractionation with concurrent chemotherapy regimens in H&N cancer. Among a series of new molecular agents under active investigation in H&N cancer, two specific examples with high promise are discussed, which exploit tumor hypoxia (tirapazamine) and overexpression of the epidermal growth factor receptor (EGFR inhibitors), respectively. These and other stepwise advances are contributing to the gradual reduction in global mortality rates for H&N cancer patients observed over the last decade, as well as to diminishing the adverse impact on patient quality of life that commonly accompanies treatment for this complex tumor site.