局部晚期鼻咽癌同步放化疗加或不加尼妥珠单抗的临床研究

Concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma:a clinical study

目的比较新辅助化疗后同步放化疗加或不加尼妥珠单抗治疗局部晚期鼻咽癌的疗效及不良反应。方法采用前瞻性研究方法,将符合入组条件的100例Ⅲ-Ⅳa期(T3N0M0期除外)局部晚期鼻咽癌患者采用随机数字表法分为试验组和对照组,两组均先行紫杉醇脂质体+顺铂+氟尿嘧啶(TPF)方案新辅助化疗2个周期。化疗后2周,试验组行同步放化疗加尼妥珠单抗靶向治疗,对照组行同步放化疗。主要观察指标为无远处转移生存(DMFS)率,主要采用log-rank检验及多因素Cox回归分析进行比较。结果试验组和对照组的客观缓解率为100%∶98%(P=1.000),完全缓解率为92.0%∶80%(P=0.084)。试验组和对照组3年DMFS率为91.4%∶76.1%,(P=0.043),3年PFS、OS、LRFS率分别为87.3%∶74.1%(P=0.097)、94.5%∶85.6%(P=0.227)、90.5%∶85.2%(P=0.444)。年龄<60岁(HR=0.34,95%CI为0.12~0.94,P=0.037),中性粒细胞/淋巴细胞比值(NLR)≤4(HR=0.34,95%CI为0.13~0.89,P=0.028)的局部晚期鼻咽癌新辅助化疗后同步放化疗加尼妥珠单抗靶向治疗的PFS更好。多因素分析发现,NLR是局部晚期鼻咽癌疾病进展(HR=5.94,95%CI为1.18~29.81,P=0.030)、远处转移(HR=13.76,95%CI为1.52~124.36,P=0.020)的独立危险因素。结论局部晚期鼻咽癌新辅助化疗后同步放化疗加用尼妥珠单抗,比不加显著提高了DMFS率,两者的不良反应发生率相当。新辅助化疗后同步放化疗加尼妥珠单抗治疗方案可能是局部晚期鼻咽癌的一个优选的治疗策略。

Objective To investigate the efficacy and side effects of concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.Methods In the prospective study,100 patients with stageⅢ-Ⅳa locally advanced nasopharyngeal carcinoma(except T3N0M0 stage)who met the inclusion criteria were randomly divided into the experimental and control groups using the random number table method.Patients in both groups were treated with neoadjuvant chemotherapy using TPF(paclitaxel liposome,cisplatin,and 5-fluorouracil)regimen for 2 cycles.At 2 weeks after chemotherapy,concurrent chemoradiotherapy plus nimotuzumab targeted therapy was given in the experimental group,and concurrent chemoradiotherapy was delivered in the control group.The main observation index was the distant metastasis-free survival(DMFS)rate.Log-rank test and multivariate Cox regression analysis were used.Results The objective remission rate and complete remission rate in the experimental and control groups were 100%vs.98%(P=1.000)and 92.0%vs.80%(P=0.084).The 3-year DMFS in the experimental and control groups were 91.4%vs.76.1%(P=0.043).The 3-year progression-free survival(PFS),locoregional recurrence-free survival(LRFS)and overall survival(OS)in two groups were 87.3%vs.74.1%(P=0.097),94.5%vs.85.6%(P=0.227)and 90.5%vs.85.2%(P=0.444).Subgroup analysis showed that patients with age<60 years(HR=0.34,95%CI=0.12-0.94,P=0.037),neutrophil-to-lymphocyte ratio(NLR)≤4(HR=0.34,95%CI=0.13-0.89,P=0.028)received concurrent chemoradiotherapy plus nimotuzumab obtained better PFS.Multivariate analysis showed that NLR was an independent risk factor for disease progression(HR=5.94,95%CI=1.18-29.81,P=0.030)and distant metastasis(HR=13.76,95%CI=1.52-124.36,P=0.020).Conclusions Compared with concurrent chemoradiotherapy alone,concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can significantly increase DMFS rate for patients with locally advanced nasopharyngeal carcinoma.The incidence of side effects is similar in two groups.Concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy may be a preferred treatment strategy for locally advanced nasopharyngeal carcinoma.