PhaseⅡstudy of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma

Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.