氯喹在Ⅳ期胶质母细胞瘤同步放化疗中的应用研究  

Application of chloroquine in postoperative concurrent chemo-radiotherapy of stage Ⅳ glioblastoma

作　　者：张旺 刘肖 杨海芳[1] 田龙[2] 胡逸民[3] ZHANG Wang;LIU Xiao;YANG Haifang;TIAN Long;HU Yimin(Radiotherapy Center,Tangshan People’s Hospital,Tangshan 063000,Hebei,China;Department of Radiotherapy,the First Affiliated Hospital of Hebei Northern University,Zhangjiakou 075000,Hebei,China;Department of Radiotherapy,Cancer Hospital Chinese Academy of Medical Sciences,Beijing 100021,China)

机构地区：[1]唐山市人民医院放射治疗中心,河北唐山063000 [2]河北北方学院附属第一医院放疗科,河北张家口075000 [3]中国医学科学院肿瘤医院放疗科,北京100021

出　　处：《癌症进展》2022年第13期1349-1352,1356,共5页Oncology Progress

摘　　要：目的探讨氯喹(CQ)在Ⅳ期胶质母细胞瘤(GBM)术后同步放化疗(CCRT)中应用的最大耐受剂量(MTD)、药代动力学及对总生存期(OS)的影响。方法采用简单随机分组法将36例Ⅳ期GBM患者分为试验组(n=18)和对照组(n=18)。对照组患者术后接受替莫唑胺(TMZ)联合放疗的CCRT,试验组患者在对照组的基础上联合CQ治疗。试验组CQ试验包括:采用贝叶斯最优区间(BOIN)设计并确定MTD和采用液相色谱-串联质谱法计算药代动力学参数。比较试验组中不同表皮生长因子受体(EGFR)表达情况患者的临床特征及生存情况,比较试验组和对照组患者的临床特征及生存情况。结果按照BOIN设计将试验组18例患者平均分为3组,每日CQ剂量分别为100、200、300 mg,最终确定200 mg为MTD。200 mg CQ组患者药代动力学主要参数:达峰时间(t_(max))为0.41(0.12~0.85)h,末端消除半衰期(t_(1/2))为(1.73±0.54)h,消除速率常数(λ_(Z))为(0.37±0.05)。试验组中EGFR(+、++、+++)患者的中位OS长于EGFR(-)患者(P=0.034),试验组患者的中位OS长于对照组(P=0.013)。结论CQ在体内吸收、消除较快。CQ联合CCRT延长了Ⅳ期GBM患者的OS,尤其是对于EGFR(+、++、+++)患者,CQ具有重要的临床价值。Objective To investigate the maximum tolerated dose(MTD),pharmacokinetics and impact on overall survival(OS)of chloroquine(CQ)in postoperative concurrent chemo-radiotherapy(CCRT)of stage Ⅳ glioblastoma(GBM).Method A total of 36 patients with stage Ⅳ GBM were randomly divided into experiment group[n=18,treated with temozolomide(TMZ)+postoperative concurrent radiotherapy+CQ]and control group(n=18,treated with TMZ+postoperative concurrent radiotherapy).CQ test for experiment group included determining MTD by Bayesian optimal interval(BOIN)design and calculating pharmacokinetics parameters by liquid chromatography coupled with tandem mass spectrometry method.Clinical characteristics and survival of patients with different expressions of epithelial growth factor receptor(EGFR)and patients in two groups were compared.Result According to BOIN design,18 patients in experiment group were divided into 3 groups on average(the daily dose of CQ was 100,200 and 300 mg),and 200 mg was finally determined as MTD.Main parameters of pharmacokinetics in patients of 200 mg CQ group included:t_(max) was 0.41(0.12-0.85)h,t_(1/2) was(1.73±0.54)h and λ_(Z) was(0.37±0.05).Median OS in patients with EGFR(+,++,+++)was significantly higher than that in patients with EGFR(-)(P=0.034),and median OS of patients in experiment group was significantly higher than that in control group(P=0.013).Conclusion CQ is absorbed and eliminated rapidly in body.CQ combined with CCRT significantly improves OS in stage Ⅳ GBM patients,especially in EGFR(+,++,+++)patients,indicating that CQ has important clinical value.

关 键 词：氯喹 Ⅳ期胶质母细胞瘤 最大耐受剂量 药代动力学 总生存期 

分 类 号：R739.41[医药卫生—肿瘤]