PD-1抑制药联合经肝动脉化疗栓塞术与酪氨酸激酶抑制药治疗不可切除肝细胞癌患者的临床研究  

Clinical trial of PD-1 inhibitor combined with transhepatic arterial chemoembolization and tyrosine kinase inhibitor in the treatment of patients with unresectable hepatocellular carcinoma

作　　者：刘迪[1] 姚维杰 吴向阳 李楠[1] 金栋[1] LIU Di;YAO Wei-jie;WU Xiang-yang;LI Nan;JIN Dong(Department of Hepatobiliary Surgery,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China)

机构地区：[1]宁夏医科大学总医院肝胆外科,宁夏回族自治区银川750004

出　　处：《中国临床药理学杂志》2023年第22期3223-3227,共5页The Chinese Journal of Clinical Pharmacology

基　　金：宁夏回族自治区科技惠民计划基金资助项目(2021CMG03015)。

摘　　要：目的观察程序性死亡受体-1(PD-1)抑制药联合经肝动脉化疗栓塞术(TACE)与酪氨酸激酶抑制药(TKI)治疗不可切除肝细胞癌(HCC)的临床疗效及其对血清血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)水平的影响。方法将HCC患者按照其治疗方案分为TACE组、TACE-TKI组和PD-1+TACE-TKI组。TACE组予以微球TACE治疗;TACE-TKI组在TACE-TKI组的基础上予以甲硫酸仑伐替尼胶囊(<60 kg者8 mg·d^(-1),≥60 kg者12 mg·d^(-1))或甲苯硫酸索拉非尼片(每次400 mg,每天2次)口服;PD-1+TACE-TKI组在TACE-TKI组的基础上予以信迪利单抗注射液(每次200 mg,每3周1次)或卡瑞利珠单抗注射液(每次200 mg,每3周1次)静脉注射,3组患者均持续干预12周。比较3组患者的临床疗效、血清VEGF、MMP-9水平,1年生存情况以及药物不良反应发生情况。结果TACE组25例,TACE-TKI组25例,PD-1+TACE-TKI组31例。治疗后,PD-1+TACE-TKI组、TACE-TKI组和TACE组的疾病控制率(DCR)分别为90.32%(28例/31例)、56.00%(14例/25例)、24.00%(6例/25例),组间两两比较差异均有统计学意义(均P<0.05);PD-1+TACE-TKI组、TACE-TKI组和TACE组的客观缓解率(ORR)分别为80.65%(25例/31例)、28.00%(7例/25例)、12.00%(3例/25例),其中PD-1+TACE-TKI组与TACE-TKI组和TACE组比较差异均有统计学意义(P<0.05),TACE-TKI组和TACE组比较差异无统计学意义(P>0.05)。治疗后,PD-1+TACE-TKI组、TACE-TKI组和TACE组的血清VEGF水平分别为(192.35±11.95)、(207.42±12.66)、(223.68±12.31)ng·mL^(-1),血清MMP-9水平分别为(1704.62±112.65)、(1761.36±114.79)、(1828.65±103.57)ng·mL^(-1),差异均有统计学意义(均P<0.05)。TACE组、TACE-TKI组、PD-1+TACE-TKI组1年生存率分别为16.00%(4例/25例)、32.00%(8例/25例)、48.39%(13例/31例),P1-1+TACE-TKI组1年生存率高于TACE组,差异有统计学意义(P<0.05)。3组的药物不良反应率比较,差异均无统计学意义(均P>0.05)。结论不可切除HCC患者应用PD-1+TACE-TKI联合治疗方案较�Objective To observe the clinical curative effect of programmed death receptor-1(PD-1)inhibitor combined with transhepatic arterial chemoembolization(TACE)and tyrosine kinase inhibitor(TKI)on unresectable hepatocellular carcinoma(HCC)and its influences on levels of serum vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9).Methods According to different treatment methods,HCC patients were divided into TACE group,TACE-TKI group and PD-1+TACE-TKI group.TACE group was given microsphere TACE treatment;TACE-TKI group was given lenvatinib metilsulfate capsules(8mg·d^(-1)for<60 kg,12 mg·d^(-1)for≥60 kg)or sorafenib tosylate tablets(400 mg once,twice a day)on the basis of TACE group.PD-1+TACE-TKI group intravenous injection of sintilimab injection(200 mg once,once every 3weeks)or camrelizumab injection(200 mg once,once every 3 weeks)on the basis of TACE group.All were intervened for 12 weeks.The clinical effect,levels of serum VEGF and MMP-9,1-year survival and the occurrence of adverse drug reactions were compared among the three groups.Results After treatment,disease control rates(DCR)in PD-1+TACE-TKI group,TACE-TKI group and TACE group were 90.32%(28 cases/31 cases),56.00%(14 cases/25 cases)and 24.00%(6 cases/25 cases);the difference between any two groups was statistically significant(P<0.05).The objective remission rates(ORR)in PD-1+TACE-TKI group,TACE-TKI group and TACE group were 80.65%(25 cases/31 cases),28.00%(7 cases/25 cases)and 12.00%(3 cases/25 cases),respectively,and there were significant differences between PD-1+TACE-TKI group and TACE-TKI group,between PD-1+TACE-TKI group and TACE group(P<0.05),but there was no significant difference between TACE-TKI group and TACE group(P>0.05).After treatment,the serum VEGF levels of PD-1+TACE-TKI group,TACE-TKI group and TACE group were(192.35±11.95),(207.42±12.66)and(223.68±12.31)ng·m L^(-1);serum MMP-9 levels were(1704.62±12.65),(1761.36±114.79)and(1828.65±103.57)ng·m L^(-1),respectively,and the differences were all statistically

关 键 词：程序性死亡受体-1抑制药 酪氨酸激酶抑制药 经肝动脉化疗栓塞术 不可切除肝细胞癌 

分 类 号：R979.1[医药卫生—药品]