Induction Chemotherapy Plus Intensity-modulated Radiotherapy Versus Concurrent Chemoradiotherapy In Nasopharyngeal Carcinoma

Background and Purpose:Concurrent chemoradiotherapy（CCRT）with a platinum-based regimen is the standard treatment for patients with locoregionally advanced nasopharyngeal carcinoma.In order to determine whether replacement of induction chemotherapy（IC）followed by Intensity-modulated radiotherapy（IMRT）alone preserve high efficacy and reduce toxicity in locoregionally advanced nasopharyngeal carcinoma in the era of IMRT,we initiated a phase II,single center,perspective,randomized,non-inferiority trial to compare the efficacy and safety of IC followed by IMRT alone versus CCRT in locoregionally advanced nasopharyngeal carcinoma.Methods:Patients with newly diagnosed stage III to IVB according to the 7^th edition of the UICC/AJCC staging system,histologically proven nonkeratinizing nasopharyngeal carcinoma were enrolled.Enrolled patients were randomized to receive IC followed by IMRT alone（IC+RT arm）,or concurrent chemotherapy plus IMRT（CCRT arm）using a random number table.Both treatment arms received the same chemotherapy regimen,which was administered as docetaxel（75 mg/m2 on day 1）plus cisplatin（25 mg/m2 per day from day 1 to3）for the first cycle and cisplatin（25 mg/m2 per day from day 1 to 3）alone for the second cycle,given intravenously with an interval of 3 weeks.Patients in the IC+RT arm commenced their radiotherapy 21 days after the first day of the second cycle of induction chemotherapy and patients in the CCRT arm commenced theirs at the first day of the first cycle of concurrent chemotherapy.The primary endpoint was progression-free survival（PFS）.Secondary end points included overall survival（OS）,locoregional recurrence-free survival（LRRFS）,distant metastasis-free survival（DMFS）,treatment response,and acute treatment toxicity.This trial was registered at the Chinese Clinical Trial Registry with the registration number of Chi CTR-TRC-14004341.Results:From June 27th,2013,to September 10th,2018,a total of 204 patients histologically diagnosed with locoregionally advanced nasopharyngeal carcinoma were enrolled in the study,with 102 patients randomly assigned to each arm.At the last follow-up date of June 25th 2020,the median follow-up duration was 45 months（range 4 to 84 months）.The3-year PFS,OS,LRRFS and DMFS were 72.2%,87.8%,92.3%and 82.7%respectively in the IC+RT arm,compared with 82.6%,92.8%,94.7%and 88.2%respectively in the CCRT arm.No statistical difference for PFS,OS,LRRFS,DMFS,or treatment response was observed between the two treatment arms（p>0.05）.The incidences of leukopenia（p=0.008）and anemia（p=0.015）were significantly higher in patients in the CCRT arm than those in the IC+RT arm.Conclusions:Compared to the standard treatment of CCRT,IC followed by IMRT alone provided similarly favorable treatment outcomes in terms of PFS,OS,LRRFS,and DMFS for patients with locoregionally advanced nasopharyngeal carcinoma,but resulted in fewer incidences of leukopenia and anemia.