**3. Role of adjuvant chemotherapy after concurrent chemoradiation**

The above-mentioned five chemoradiation trials used adjuvant chemotherapy also. Hence the benefit of adjuvant chemotherapy when added to chemoradiation is not clear. Moreover, with the advancements in radiation techniques, the local control has increased significantly and distant metastasis remains the common mode of failure. This prompted investigators to test the value of adjuvant chemotherapy when added to chemoradiation. Chen et al randomized stage III and IV nonmetastatic non-keratinizing NPC patients to concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone. Cisplatin 40 mg/m2 weekly was used as the concurrent regimen. Adjuvant chemotherapy consisted of 3 cycles of cisplatin 80 mg/m on day 1 and 5FU 800 mg/m2 per day on days 1–5. After a median follow-up of 37·8 months, the 2 year FFS was 86% in the adjuvant chemotherapy group compared to 84% in the CCRT group(p = .13). There was no significant difference in Overall survival, Distant failure-free survival, and loco-regional failure-free survival [17]. The update also showed similar results [18]. The outcomes in the two arms were similar irrespective of the radiotherapy technique (2D vs 3Dvs IMRT). All three cycles of adjuvant chemotherapy were completed by only 63% of patients in the adjuvant arm.

Adjuvant chemotherapy after concurrent chemoradiation is associated with significant toxicities and poor compliance without any survival advantage. There is no evidence to recommend routine use of adjuvant chemotherapy in locally advanced NPC.

#### **4. Adjuvant chemotherapy-risk adjusted treatment**

EBV is related to NPC in endemic areas. EBV DNA load has been correlated with the prognosis of NPC in many studies [19, 20]. Hong Kong 0502 trial included patients with detectable plasma EBV DNA after curative radiotherapy. Patients were randomized to adjuvant chemotherapy with cisplatin-gemcitabine or observation [20]. After a median follow-up of 6.6 years, there was no significant difference in the 5-year relapse-free survival (RFS) rate between the two arms (49.3% versus 54.7%; HR 1.09, P = 0.75).

#### **5. Induction chemotherapy in NPC**

Concurrent chemo-RT with advanced radiotherapy techniques have increased the locoregional control in locally advanced NPC. But distant metastasis continued


**Table 1.**

*Phase 3 trials of induction chemotherapy in locally advanced nasopharyngeal carcinoma.*
