Induction Therapy of Nituzumab Combined PF Regimen to Improve the Treatment Response and Tolerance of Locally Advanced Nasopharyngeal Carcinoma Undergoing the Concurrent Chemoradiotherapy: A Multi-Center Controlled Randomized Clinical Study

Abstract

The role of targeted combined with chemotherapy-based induction therapy in locally advanced nasopharyngeal carcinoma with concurrent intensity-modulated radiotherapy(IMRT) is unclear. Through a multi-center randomized controlled study to investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen (cisplatin + 5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. From January 2015 to November 2017，We included 118 patients with stage III-IVa nasopharyngeal carcinoma from 8 tumor centers, 58 cases in NPF group (induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group (induction chemotherapy of docetaxel, cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received cisplatin concurrent intensity-modulated radiotherapy (IMRT), and the safety and short-term efficacy of the two groups were compared. To analyze the correlation between the curative effect of induction therapy and EGFR expression. Until May 2018, all patients were treated and evaluated immediately after treatment. Compared with the TPF regimen , the nimotuzumab combined PF scheme was more effective for the cervical lymph node (p=0.036), and the response rate (CR+PR) was higher (60% vs 81%) , but there was no statistically significant difference in the curative effect of nasopharyngeal lesion and induction therapy (p=0.446,p=0.143); there was no statistically significant difference in immediate curative effect (p=0.449). Compared with the TPF group, although the incidence of 1 grade rash was significantly increased (p=0.012), the neutropenia and gastrointestinal reaction of NPF group was significantly reduced, the difference was statistically significant (p=0.028;p=0.049).The treatment tolerance of cisplatin during the IMRT stage is better in the NPF group, the gastrointestinal reaction, oral mucositis and radiation dermatitis were significantly reduced, and the difference was statistically significant (p=0.038,p=0.041,p=0.035).The expression rate of EGFR in the whole group was 94.9%. Compared with chemotherapy, patients with EGFR high expression can get a better treatment response (P=0.033) from the induction treatment of nituzumab monoclonal combined chemotherapy. For the locally advanced nasopharyngeal carcinoma patients received treated with cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen has a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiochemotherapy , but the long-term efficacy requires further follow-up observation. Patients with EGFR high expression may gain more benefits from the induction treatment of EGFR combined chemotherapy.