For stage III and locally confined stage IV disease, 50% to 80% develop recurrent or metastatic disease within 5 years of treatment with radiotherapy alone. Whilst chemotherapy was used only for palliation of metastatic disease in the past, it has now become an integral part of treating locally advanced NPC.

Many chemotherapeutic agents have shown significant activity in NPC including bleomycin, methotrexate, 5-fluorouracil, Platinum analogues, paclitaxel and more recently, gemcitabine and docetaxel. The most widely used chemotherapy regimen is the combination of 5-fluorouracil and cisplatin, which was reported to give a response rate of 55% to 60%. New combinations like paclitaxel and carboplatin; gemcitabine and cisplatin, have also shown comparable efficacy in many studies.

Despite recent advances in multi-modality management, radiotherapy remains the cornerstone in treating locally confined NPC. Using chemotherapy in this setting is aimed at enhancing and complementing radiation. Administrating chemotherapy with radiation exploits the radiosensitizing property of drugs like 5-fluorouracil and cisplatin.

In a study conducted in US, Al-Sarraf et al showed significant survival advantage when patients were treated with concurrent chemo-radiotherapy followed by adjuvant chemotherapy versus radiotherapy alone. Wee et al arrived at the same conclusion when 221 patients with endemic NPC were treated at the National Cancer Centre, Singapore, using a similar protocol.

The role of neoadjuvant (before radiotherapy) and adjuvant (after radiotherapy) chemotherapy is less well defined. By giving full dose chemotherapy, aside from concurrent chemo-radiotherapy targeted at local control, there is theoretical advantage of reducing metastasis.

Studies on neoadjuvant chemotherapy have had conflicting results and have not convincingly demonstrated significant benefit. Similarly, studies exploring adjuvant chemotherapy have also not supported routine use of the strategy in treating locally advanced NPC.

Radiotherapy continues to be the definitive treatment for early stage (stage I/II) NPC. Concurrent chemo-radiotherapy is now considered treatment of choice in locally advanced (stage III and IVA/B) disease while the addition of neoadjuvant or adjuvant chemotherapy remains investigational.