Meta‐Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma

PURPOSE: Concurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA‐NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta‐analysis investigates the value of adding ICT to CCRT in LA‐NPC. MATERIALS AND METHODS: Two reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment‐naive adult patients with histologically proven nonmetastatic LA‐NPC. RESULTS: Eight RCTs with in total 2,384 randomized patients, of whom 69% had N2–N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%–100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) –0.001–0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, −0.243; 95% CI, −0.403 to −0.083; p = .003). Grade 3–4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511–0.905; p = .001) and progression‐free survival (HR, 0.657; 95% CI, 0.568–0.760; p < .001). CONCLUSION: Although ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA‐NPC, but further study on optimal patient selection for this treatment is warranted. IMPLICATIONS FOR PRACTICE: Locally advanced nasopharyngeal carcinoma (LA‐NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta‐analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA‐NPC is associated with a significant clinical improvement in both overall survival and progression‐free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA‐NPC.