Current Treatment Options in the Management of Locally Advanced Squamous Cell Cancers of Head and Neck

Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median 5-year overall survival of approximately 40-60%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. The curative treatment of locally advanced head and neck squamous cell cancer has been advanced greatly with the establishment of chemotherapy. More recently, Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has been approved in combination with RT in patients with locally advanced HNSCCs. Researchers have focused on other monoclonal antibodies against EGFR (Zalutumumab, Nimotuzumab), anti-angiogenic agents (Bevacizumab), tyrosine kinase inhibitors (gefitinib, erlotinib, sorafenib, sunitinib), Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR, monoclonal antibodies against EGFR (Zalutumumab, Nimotuzumab), CUDc-101, a mutli-targeted agent against histone deacetylase (HDAC), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors are currently being tested in different phases of clinical trials. Other treatments modalities like gene therapy and immune therapy has shown promise in the management of these cancers.

Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The discovery of human papilloma virus (HPV) as a prognostic tool is likely to change the landscape of treatment of HNSCCs. The current chapter focuses on insight into current treatment options in the management of locally advanced head and neck cancers and updates on the clinical trials and patents using new investigational agents in the management for HNSCCs.

Keywords: Cetuximab, cisplatin, CRT, EGFR, erlotinib, gefitinib, head and neck squamous cell cancers, head-shock protein, hypoxia, human papilloma virus, immunotherapy, intensity modulated radiation therapy, lonafarnib, nimotuzumab, Phase III, proteosome inhibitors, sorafenib, vandetanib, VEGF, zalutumumab.