Drug Therapy for Nasopharyngeal Carcinoma: Cytotoxic and Targeted Therapy

Nasopharyngeal carcinoma (NPC) occurring in endemic areas such as Southern China and Southeast Asia are typically nonkeratinizing, undifferentiated, or poorly differentiated squamous cell carcinoma. These histological subtypes are characterized by their susceptibility to cytotoxic chemotherapy and association with Epstein—Barr virus (EBV) infection. In Hong Kong, where the annual incidence rate of NPC is around 20/100,000 persons, the stage distribution at diagnosis is reportedly 48% for early stage NPC (American Joint Committee for Cancer, AJCC stages I and II (2002)), and 52% for advanced NPC (stages III and IV) (Lee et al. 2005). In a multi-institutional review by the Hong Kong Nasopharyngeal Cancer Study Group of over 2,600 NPC patients treated between 1996 and 2000, the 5-year overall survival rate for stage I and II NPC reached 85% following radiotherapy alone, whereas only 66% of patients with nonmetastatic stage III and IVB NPC remained alive 5 years after radical radiotherapy (Lee et al. 2005). This poor outcome is mainly attributed to the fact that over 30% of patients with stage III to IV NPC relapse at distant sites following radiotherapy, where the median overall survival is only 12–18 months (Ma et al. 2008). Cytotoxic chemotherapy plays an important role in the curative and palliative treatment of advanced NPC. This chapter provides an overview of the clinical development of cytotoxic and targeted therapy in endemic NPC, and the impact of drug therapy on the clinical outcome of NPC over the last two decades. Particular attention will be given to the historical development of platinum and nonplati-num chemotherapy, and also targeted therapies against the epidermal growth factor receptor (EGFR), tumor angiogenesis, and epigenetic mechanisms of the control of gene expression in NPC.