Chemotherapy in head and neck squamous cell cancer

Abstract

This chapter will outline the application of chemotherapy in head and neck squamous cell carcinoma (HNSCC) chronicling the evolution of treatment since its inception at the hands of Paul Ehrlich in the late 1800s. We will discuss the discoveries in cancer kinetics and the clinical trials that have established the current standards of treatment and conclude with a discussion of ongoing research endeavors. Surgical excision has remained the mainstay of curative efforts over the years. Contrary to many other cancers, HNSCC treatment failure tends to occur with locoregional recurrence. The addition of radiation therapy to advanced stage tumors and/or those with high-risk features has improved outcomes; adding chemotherapy in select cases has further improved our ability to treat HNSCC patients. By targeting rapidly dividing cancer cells, and more recently targeting-specific molecular signaling pathways of cancer cells, chemotherapy has become an important part in treatment of advanced stage HNSCC and remains the key player in palliative therapy of metastatic disease. Generally employed as adjuvant treatment together with radiation to improve locoregional control and prevent recurrence, concurrent chemoradiation therapy can also serve as organ preservation therapy in an attempt to avoid surgical removal of vital structures. Despite many clinical trials evaluating variations in chemotherapy modalities and agents, the standard of care has remained largely unchanged over the last 15 years. The emergence of HPV+ tumors has garnered much attention in the media, and while these tumors appear to behave differently and add further research questions, the publicity has sparked a tremendously needed increase in conversation about HNSCC and the gap in our ability to treat it. Recent research advances have positioned us on the horizon of a new field of chemotherapy that includes biotherapies such as the already utilized antibody cetuximab and T cell receptor ligands such as PD-L1, which is currently the subject of clinical trials for HNSCC and other late-stage solid tumors. Hope remains that as our understanding of the molecular biology of cancer evolves, an increasing array of agents including those targeting-specific molecular signaling pathways unique to cancer cells will become available.