示踪用盐酸米托蒽醌注射液用于甲状腺癌前哨淋巴结示踪的临床疗效、安全性及药代动力学Ⅰ期试验  

Clinical Efficacy,Safety and Pharmacokinetics of Tracing Injection of Mitoxantrone Hydrochloride for Tracing Sentinel Lymph Nodes in Thyroid Carcinoma:A PhaseⅠClinical Trial

作　　者：陈少博 刘玮楠[2] 张圣洁 孙健[4] 杨瑞 王淑君[6] 陈革[2] CHEN Shaobo;LIU Weinan;ZHANG Shengjie;SUN Jian;YANG Rui;WANG Shujun;CHEN Ge(Department of Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of General Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Operating Room,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;College of Chinese Medicine,Shenyang Pharmaceutical University,Shenyang 110000,China;College of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110000,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院外科,北京100730 [2]中国医学科学院,北京协和医学院,北京协和医院基本外科,北京100730 [3]中国医学科学院,北京协和医学院,北京协和医院手术室,北京100730 [4]中国医学科学院,北京协和医学院,北京协和医院病理科,北京100730 [5]沈阳药科大学中药学院,沈阳110000 [6]沈阳药科大学药学院,沈阳110000

出　　处：《协和医学杂志》2021年第5期729-735,共7页Medical Journal of Peking Union Medical College Hospital

摘　　要：目的探究示踪用盐酸米托蒽醌注射液在甲状腺癌根治术中对淋巴结染色、示踪的效果及其安全性和耐受性。方法本研究采用单中心、开放、空白对照试验设计,按剂量递增原则,逐剂量组进行人体耐受性试验和药代动力学试验。前瞻性纳入2016年12月至2017年3月北京协和医院拟行甲状腺癌根治术的患者为受试者,并分为空白对照组和试验组。空白对照组进行常规手术,不注射示踪剂;试验组暴露术野后拟分别在甲状腺腺体注射0.2 mL、0.4 mL、0.6 mL、0.8 mL、1.2 mL示踪用盐酸米托蒽醌注射液,由低至高依次进行5个剂量组的爬坡试验。主要疗效指标为淋巴结示踪率和淋巴结染色率,次要疗效指标为淋巴结染色程度评分和示踪持续成功率。记录给药后受试者体征变化,进行安全性评定。给药前及给药后10 min、20 min、30 min、60 min、90 min、120 min,分别采集受试者静脉血计算药代动力学参数。结果共纳入27例受试者,其中空白对照组3例;试验组0.2 mL、0.4 mL、0.6 mL、0.8 mL、1.2 mL 5个剂量组分别为3例、3例、6例、6例、6例。当试验进行至第3个剂量组(0.6 mL)时,受试者注射部位对药物注射剂量承载已达饱和,终止试验,故实际共15例受试者完成试验。空白对照组均未出现淋巴结染色。试验组中,12例受试者中央区淋巴结全部染色,部分侧颈部淋巴结也出现染色,甲状旁腺不被染色、呈负显影。0.2 mL、0.4 mL、0.6 mL剂量组给药前后淋巴结染色程度评分存在显著性差异(P<0.05),平均淋巴结染色率分别为90.47%、91.67%、91.36%,平均淋巴结示踪率分别为79.17%、100%、98.67%。试验组淋巴结清扫持续时间为5~20 min,均未出现染色的淋巴结褪色,示踪持续成功率为100%。安全性评价中,空白对照组和试验组均未发生严重不良事件,且不良事件发生原因与该示踪剂肯定无关。药代动力学试验显示,该示踪经剂经腺�Objective To investigate the staining and tracing effect of mitoxantrone hydrochloride injection for tracing lymph nodes in radical thyroidectomy,and its safety and tolerability.Methods In this study,a single-centered,open-labeled,blank control trial was designed.According to the principle of dose escalation,the human tolerance test and kinetic test were performed in dose groups one by one.Patients scheduled for radical thyroidectomy in Peking Union Medical College Hospital from December 2016 to March 2017 were prospectively enrolled as subjects.The subjects were divided into the blank control group and the test groups.The blank control group routinely underwent surgery without tracer injection;the test groups were injected with 0.2 mL,0.4 mL,0.6 mL,0.8 mL,or 1.2 mL of mitoxantrone hydrochloride for tracing in the thyroid gland after exposing the surgical field,and an escalation test was performed in the five dose groups from low to high.The primary efficacy measures were lymph node tracing rate and lymph node staining rate;the secondary efficacy measures were staining-degree scores of lymph nodes and the success rate of tracing persistence.Changes in signs of subjects were recorded for safety assessment.Venous blood was collected from the subjects before administration and at 10 min,20 min,30 min,60 min,90 min and 120 min after administration to calculate the kinetic parameters.Results A total of 27 subjects were included,including 3 subjects in the blank control group,and 3,3,6,6 and 6 subjects in the 0.2 mL,0.4 mL,0.6 mL,0.8 mL and 1.2 mL dose group,respectively.When the test proceeded to the third dose group(0.6 mL),the injection site of the subjects was saturated with the injection dose,and the test was terminated.Therefore,a total of 15 subjects completed the test.No lymph node was stained in blank control group.The lymph nodes of 12 subjects showed blue staining,and the parathyroid glands were not stained and negatively visualized.There was significant difference in the staining-degree scores of lymph node

关 键 词：示踪用盐酸米托蒽醌注射液 甲状腺癌 淋巴结 

分 类 号：R736.1[医药卫生—肿瘤]