Four cycles of docetaxel plus cisplatin as neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in stage N2-3 nasopharyngeal carcinoma: phase 3 multicentre randomised controlled trial.

OBJECTIVE: To compare the effects of four cycles of docetaxel with cisplatin as a neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with concurrent chemoradiotherapy alone by assessing reductions in distant metastasis and improvements in survival in patients with stage N2-3nasopharyngeal carcinoma. DESIGN: Phase 3, multicentre, randomised controlled trial. SETTING: Six sites in China from 23 February 2016 to 18 February 2019. PARTICIPANTS: 186 participants aged </=70 years with a diagnosis of untreated stage T1-4N2-3M0 nasopharyngeal carcinoma. INTERVENTION: Participants were prospectively enrolled and randomly allocated to either the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group (four cycles of neoadjuvant chemotherapy (docetaxel 75 mg/m(2) on day 1 and cisplatin 37.5 mg/m(2) on days 2-3, every 3 weeks) followed by concurrent chemoradiotherapy (intensity modulated radiotherapy plus weekly cisplatin 40 mg/m(2)) or the concurrent chemoradiotherapy only group, in a 1:1 ratio. MAIN OUTCOME MEASURES: Five year distant metastasis-free survival and overall survival were analysed using the intention-to-treat approach. RESULTS: 93 participants were assigned to each of the neoadjuvant chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy only groups. After a median follow-up time of 76.9 (interquartile range 65.4-85.9) months, the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group had superior five year distant metastasis-free survival (91.3% (95% confidence interval (CI) 85.4% to 97.2%) versus 78.2% (69.8% to 86.6%); hazard ratio 0.41 (95% CI 0.19 to 0.87); P=0.02) and five year overall survival (90.3% (84.2% to 96.4%) versus 82.6% (75.0% to 90.2%); hazard ratio 0.38 (0.18 to 0.82); P=0.01). Grade 3/4 acute toxicities were observed in 60 (65%) and 46 (51%) patients in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy only groups, respectively (P=0.05). The higher acute toxicity observed in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group was primarily due to grade 3/4 neutropenia (43 (47%) v 10 (11%); P<0.001). No significant difference in any late toxicity was observed between the two groups, and participants in the neoadjuvant chemotherapy plus concurrent chemoradiotherapy group tended to have a better quality of life five years after enrolment. CONCLUSIONS: Four cycles of docetaxel plus cisplatin neoadjuvant chemotherapy with concurrent chemoradiotherapy can effectively reduce distant metastasis and improve survival for patients with stage N2-3 nasopharyngeal carcinoma with manageable toxicities. TRIAL REGISTRATION: ClinicalTrials.gov NCT02512315.