尼妥珠单抗联合放化疗治疗儿童脑干胶质瘤的临床研究

Clinical study of nimotuzumab combined with chemoradiotherapy in the patients with pediatric brain stem gliomas

背景与目的:儿童脑干胶质瘤预后差,生存期短,严重威胁儿童生命。大多数神经胶质瘤表皮生长因子受体(epidermal growth factor receptor,EGFR)过表达,而尼妥珠单抗是专门针对EGFR的治疗性药物,探讨该药联合放化疗对儿童脑干胶质瘤的疗效和不良反应。方法:作为开放式随机对照单中心研究,选取2010年1月—2014年12月在上海交通大学医学院附属新华医院就诊的经影像学或病理学检查证实的儿童脑干恶性肿瘤20例,分为3组,第1组7例,尼妥珠单抗联合放化疗;第2组7例,放化疗;第3组6例,单纯放疗。结果:应用尼妥珠单抗者仅4例出现血液学毒性,2例恶心,1例发热,均为Ⅰ/Ⅱ级。第1组至第3组的中位总生存期(overall survival,OS)依次为11.6、9.7和7.1个月,3组生存曲线的差异有统计学意义(Log-rank P=0.008)。第1组至第3组的中位OS依次为12.1、8.1和5.8个月,3组生存曲线的差异有统计学意义(Log-rank P=0.015 2)。高级别患者接受尼妥珠单抗治疗者中位OS为12.1个月,而未接受尼妥珠单抗治疗者中位OS为7.1个月,生存曲线的差异有统计学意义(P=0.011 9)。对部分缓解(partial remission,PR)率的统计学分析显示,各组差异均无统计学意义。结论:尼妥珠单抗联合放化疗对儿童脑干胶质瘤患儿具有良好的疗效,能显著地改善患儿预后和延长生存期,但该结果需要在更大样本的研究中进行验证。

Background and purpose:The prognosis of brain stem glioma in children is poor,which is a serious threat to children’s lives.Most gliomas are overexpressed with epidermal growth factor receptor(EGFR),and nimotuzumab is a therapeutic drug specifically binding to EGFR.This study was to investigate the efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy in patients with brain stem gliomas in children.Methods:From January 2010 to December 2014,20 children with brain stem glioma confirmed by imaging or pathology in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were randomly divided into 3 groups.Seven patients with brain stem glioma in group 1 were treated with nimotuzumab combined with chemoradiotherapy.Seven patients in group 2 were treated with radiotherapy and chemotherapy,and 6 patients in group 3 were treated with radiotherapy alone.Results:The hematological toxicity occurred in only 4 cases,nausea in 2 cases and fever in 1 case,and all of which were gradeⅠ/Ⅱ.The median overall survival(OS)for group 1,2 and 3 was 11.6,9.7 and 7.1 months,respectively.There was a significant difference in survival curve among the three groups(Log-rank P=0.008).The median OS of high grade gliomas for group 1,2 and 3 was 12.1,8.1 and 5.8 months,respectively.There was a significant difference in survival curve among the three groups(Log-rank P=0.015 2).The median OS was 12.1 months in the patients with high-grade glioma treated with nimotuzumab and 7.1 months without nimotuzumab.The difference between the two survival curves was statistically significant(P=0.011 9).Partial remission(PR)rates showed no statistical significant difference in this study.Conclusion:Nimotuzumab combined with chemoradiotherapy can significantly improve the prognosis and prolong overall survival of children with brain stem glioma.However,the results need to be verified in a study with larger sample size.