LAUSR

There were approximately 87,000 reported cases of nasopharyngeal carcinoma (NPC) and approximately 51,000 deaths from NPC worldwide in 2012. NPC is more commonly seen among the Asian population verus the Western population. In 2013, an estimated 42,100 new cases and 21,320 deaths were attributed to NPC in China. The crude incidence and mortality rates of NPC are 3.09 per 100,000 but can rise up to 21 per 100,000 in certain hotspot regions in China. In the United States, NPC is quite rare with <1 case for every 100,000 people each year. Because the majority of these patients present with locoregionally advanced (LA) disease and surgery is not part of its upfront management, patients are treated with a combination of chemotherapy and definitive radiation therapy. Since the publication of the Intergroup 0099 trial, the incorporation of chemotherapy into the backbone of definitive radiation therapy has become the de facto standard for nonmetastatic, LA NPC in the United States. Patients undergo 3 cycles of concurrent high-dose cisplatin (100 mg/m) on days 1, 22, and 43 of radiation (to 70 Gy), followed by 3 additional cycles of adjuvant cisplatin (80 mg/m) and 5-fluorouracil (5-FU; 1000 mg/m). In Singapore, Wee et al conducted a trial virtually identical in design to the US Intergroup study and validated the US findings. The Hong Kong NPC study group has also recently reproduced the US Intergroup study design in 2 separate randomized studies for patients with NPC, and found substantial improvements in failure-free survival and progression-free survival (PFS) with a trend toward an improvement in overall survival (OS). Exploratory analyses of 2 large NPC trials from Hong Kong have also shown that the use of adjuvant chemotherapy reduces distant metastasis and that the number of delivered cycles (3-4 vs 0-1) is critical for decreasing distant failures. Lin et al in a subsequent re-analysis of their randomized NPC trial in Taiwan showed that the benefit of concurrent chemoradiation alone without adjuvant chemotherapy was not observed in patients who were at very high risk for developing distant metastasis. Lastly, although randomized NPC trials comparing concurrent chemoradiation with no adjuvant chemotherapy to radiation alone have shown improvement in OS, a closer look at these trials has shown inadequate control of distant disease. Since these publications, there have been numerous studies, including a number of meta-analyses from both the Eastern world and the Western world, that continue to show the added benefit of using adjuvant chemotherapy with radiation or chemoradiation. In fact, the addition of adjuvant chemotherapy after concurrent chemoradiation produces the highest survival benefit and consistent improvements for all endpoints even in comparison with induction chemotherapy followed by concurrent chemotherapy. An update of the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) analysis continues to show that concurrent chemoradiation alone is insufficient to combat distant metastasis of LA NPC and that additional chemotherapy, whether induction or adjuvant, is necessary to improve patient survival. Adjuvant chemotherapy continues to produce the biggest improvement in survival, with neoadjuvant chemotherapy trailing not far behind. Because of the difficulty in delivering an additional 3 cycles of adjuvant chemotherapy after 7 weeks of concurrent chemoradiation and because of the understanding that more chemotherapy is needed in addition to concurrent chemoradiation, there is a renewed interest in bringing back neoadjuvant chemotherapy as a standard approach for LA NPC. The ease of administering induction chemotherapy from the prescriber’s point of view in comparison with adjuvant chemotherapy has further rekindled the desire to pursue this neoadjuvant approach. The assumption is that induction chemotherapy is better tolerated and overcomes the poor tolerance of patients for adjuvant chemotherapy. Although there is no survival benefit from induction chemotherapy for head and neck squamous cell carcinoma, several recent randomized studies from the Sun Yet Sen Cancer Center have shown improvements in survival when induction chemotherapy (docetaxel, cisplatin, 5-FU, or gemcitabine and cisplatin) is given before concurrent cisplatin and radiation in comparison with cisplatin