**Abstract**

Nasopharyngeal carcinoma is a unique disease entity among head and neck cancers due to its epidemiology and clinical behavior. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the treatment for early-stage disease. With the widespread use of IMRT, loco-regional control has improved significantly in locally advanced diseases. But distant metastasis continues to be the most common pattern of failure. To address this issue, chemotherapy has been incorporated into radiotherapy in various settings; as concurrent, induction, and adjuvant. The initial trials of concurrent chemotherapy incorporated adjuvant chemotherapy also and the magnitude of benefit contributed by each treatment was not clear. Later trials proved that adjuvant chemotherapy was not beneficial. Induction chemotherapy when added to concurrent chemoradiation resulted in improvement in Failure Free Survival, Overall Survival, and Distant Metastasis Free Survival. Thus, induction chemotherapy followed by concurrent chemoradiation became the standard of care for locally advanced disease (stage III and IVA). The role of chemotherapy in stage II disease is still evolving. Metastatic nasopharyngeal carcinoma is treated by platinum doublet chemotherapy, Cisplatin-gemcitabine is the standard regimen.

**Keywords:** Nasopharyngeal carcinoma, locally advanced, metastatic, concurrent chemotherapy, induction chemotherapy, adjuvant chemotherapy

## **1. Introduction**

Nasopharyngeal carcinoma (NPC) is unique from other head and neck cancers due to its difference in epidemiology, etiology and propensity for distant metastasis. It is endemic in Southern China, South East Asia, North Africa, and Artic region. Non-keratinizing or undifferentiated carcinoma is the most common histological type in endemic areas. Radiotherapy is the backbone of treatment owing to the complex anatomical location and high radiosensitivity. Higher local control and survival are reported for early-stage disease with radiotherapy alone [1]. But around 70% of patients present with locoregionally advanced disease and outcomes with radiotherapy alone are poor [2]. Many strategies have been tried to improve outcomes in locoregionally advanced NPC; the incorporation of chemotherapy and the use of modern radiotherapy techniques. IMRT when compared with two-dimensional

radiotherapy showed significantly better locoregional control and survival with a lower incidence of radiation- induced toxicities [3, 4]. IMRT is mainly aimed at reducing the toxicities in the early stages whereas it improves loco-regional control (LRC) in advanced stages. After the widespread use of IMRT, distant metastasis remains the predominant pattern of failure. Hence chemotherapy was added to radiotherapy in various settings; as concurrent, induction, and adjuvant. Patients with metastatic disease are treated by palliative chemotherapy or palliative radiotherapy.
