Induction chemotherapy in nasopharyngeal carcinoma- A systematic review of phase III clinical trials

Background: : Induction Chemotherapy (IC) has the potential advantage of resulting in early eradication of micro metastasis thereby reducing distant failure in Nasopharyngeal Carcinoma (NPC). This study is to evaluate the effectiveness of induction chemotherapy in NPC based on published phase III Randomized Controlled Trials (RCT) Methods: : We searched PubMed, SCOPUS, EMBASE and COCHRANE databases for phase III trials evaluating the role of IC in NPC using the following key words: nasopharyngeal carcinoma, locally advanced, locoregionally advanced, induction chemotherapy, and concurrent chemoradiation. We included phase 3 RCTs of NPC in which intervention patients received induction chemotherapy plus concurrent chemoradiation (CCRT) and the control patients received CCRT alone. Results: : Six phase III RCTs have reported the data on effectiveness of IC in NPC so far. All except one study found statistically significant improvement in the primary outcome. One study demonstrated improved relapse free survival (RFS) with IC (stratified HR for recurrence or death 0.51; p=0.0001). Two studies reported improvement in disease free survival (DFS) with IC [adjusted HR 0.739 (p=0.0264) in one study; HR for 3-year and stratified HR for 5-year DFS 0.67 (p=0.028) and 0.66 (p=007) respectively in the other study]. One study demonstrated improvement in failure free survival (FFS) with IC [HR for 3-year and 5-year FFS 0.68 (p=0.034) and 0.67 (p=0.019) respectively] and another study reported improved progression free survival (PFS) [HR 0.44; p=0.042)]. Grade 3-4 acute adverse events were higher among patients who received IC. Conclusion: : IC followed by CCRT showed superior clinical outcomes in NPC compared to CCRT alone. Conflicting results were found with regard to overall survival.