The majority of nasopharyngeal carcinoma (NPC) patients present at locally advanced stage. The poor prognosis has led to increasing interests in exploring the use of chemotherapy (CT). Intergroup-0099 trial was the first randomized trial comparing concurrent chemoradiotherapy (CCRT) with radiotherapy (RT) alone. Its outcome established the treatment standard in the United States as standard of care for locally advanced NPC. However, criticism has been arisen, particularly about its reproducibility and applicability in Southeast Asia where NPC is an endemic disease. Subsequently, new evidence has been provided by a large number of publications from various centers. In this article, through comprehensively analyzing recent meta-analyses and randomized controlled trials performed in Asian centers, we conclude that CCRT as a treatment paradigm is also applicable to patients in Southeast Asia and should be standard of practice in locally advanced disease. However, the CT regimen varied markedly among those trials, and the optimal regimen and scheduling remains to be determined. Moreover, a number of patients experienced toxicities and the treatment compliance was generally poor. With the emergence of new RT techniques such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), the role of concurrent CT with these new techniques needs to be tested. New chemotherapeutics have been investigated in the recurrent or metastatic disease. However, their effectiveness in previously untreated NPC is unclear. Previous efforts have been made for immunotherapy and targeted therapy in palliative setting. Their role in newly diagnosed NPC should be evaluated, particularly when they are combined with CT or RT.

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