阿昔替尼联合替雷利珠单抗在一线靶向治疗失败的晚期肾癌患者中的疗效观察  

Efficacy of axitinib combined with tislelizumab in the treatment of patients with advanced renal cell carcinoma who failured first-line targeted therapy

作　　者：吴岑[1] 黄志扬[1] 伍伯聪[1] 张文彬[1] 陈希 吕联辉[1] 黄应福[1] 郑志雄[1] WU Cen;HUANG Zhi-yang;WU Bo-cong;ZHANG Wen-bin;CHEN Xi;LÜLian-hui;HUANG Ying-fu;ZHENG Zhi-xiong(Department of Urology,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属泉州第一医院泌尿外科,福建泉州362000

出　　处：《中国临床药理学杂志》2021年第12期1501-1504,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察阿昔替尼联合替雷利珠单抗在一线靶向治疗失败的晚期肾细胞癌(肾癌)治疗中的临床疗效和安全性。方法入选一线靶向治疗失败晚期转移性肾癌患者10例。予以序贯联合治疗方案,即阿昔替尼5 mg bid,连续口服,替雷利珠单抗200 mg静脉滴注,每3周1次,治疗持续至肿瘤进展或因发生可能威胁生命的毒性反应退出为止。于治疗前及接受治疗2个周期后,用酶联免疫吸附法检测血清中肿瘤坏死因子-β1(TNF-β1)、血管内皮生长因子(VEGF)、金属蛋白酶-1组织抑制剂(TIMP-1)、基质金属蛋白酶-2(MMP-2)水平,评价患者疗效与药物不良反应发生情况。结果10例患者均可评价疗效,其中未见完全缓解(CR),部分缓解(PR)占60.00%(6例/10例),疾病稳定(SD)占20.00%(2例/10例),疾病进展(PD)占20.00%(2例/10例),疾病控制率(DCR)为80.00%(8例/10例),客观缓解率(ORR)为60.00%(6例/10例)。患者治疗前TNF-β1、VEGF、TIMP-1、MMP-2水平分别为(45.35±5.61)μg·L^(-1),(37.82±4.97)ng·L^(-1),(82.41±8.49)pmol·L^(-1),(185.24±26.61)μg·L^(-1),治疗2周期后数值分别为(21.89±3.62)μg·L^(-1),(16.63±2.75)ng·L^(-1),(36.00±5.81)pmol·L^(-1),(57.26±5.38)μg·L^(-1),差异均有统计学意义(均P<0.01)。患者所出现的药物不良反应主要为ⅠⅡ度,且以乏力、高血压、口腔黏膜炎、腹泻、甲状腺功能减退、手足综合征、高胆固醇血症、声音嘶哑等多见,对症处理后好转,患者耐受良好。结论在一线靶向治疗失败后,给予阿昔替尼与替雷利珠单抗序贯联合治疗晚期肾癌的效果显著,在一定程度上抑制肿瘤的增殖及浸润,安全性事件总体可控,可以作为一线靶向治疗进展后的后线治疗。Objective To observe the clinical efficacy and safety of axitinib combined with tislelizumab in the treatment of advanced renal cell carcinoma(RCC)with failed first-line targeted therapy.Methods Ten patients with advanced metastatic renal cell carcinoma who failed to receive first-line targeted therapy were given sequential combination therapy:axitinib 5 mg bid,orally,tislelizumab 200 mg intravenously,once every 3 weeks.The treatment lasted until the tumor progressed or withdrew due to potential life-threatening toxic reactions.The serum levels of tumor necrosis factor-β1(TNF-β1),vascular endothelial growth factor(VEGF),tissue inhibitor of metalloproteinase-1(TIMP-1)and matrix metalloproteinase-2(MMP-2)were detected by enzyme-linked immunosorbent assay before and after two cycles of treatment.The efficacy and the incidence of adverse reactions was analyzed.Results The efficacy of patients could be evaluated,and no complete remissions(CR)was found,parital response(PR)was 60.00%(6 cases/10 cases),stable disease(SD)was 20.00%(2 cases/10cases),progressive disease(PD)was 20.00%(2 cases/10 cases),disease control rate(DCR)was 80.00%(8cases/10 cases),objective response rate(ORR)was 60.00%(6 cases/10 cases).The levels of TNF-β1,VEGF,TIMP-1 and MMP-2 before treatment were(45.35±5.61)μg·L^(-1),(37.82±4.97)ng·L^(-1),(82.41±8.49)pmol·L^(-1),(185.24±26.61)μg·L^(-1),and after two cycles of treatment,which were(21.89±3.62)μg·L^(-1),(16.63±2.75)ng·L^(-1),(36.00±5.81)pmol·L^(-1),(57.26±5.38)μg·L^(-1),all with significant difference(all P<0.01).The adverse reactions of the whole group were mainly gradeⅠ-Ⅱ,and most of them were fatigue,hypertension,oral mucositis,diarrhea,hypothyroidism,hand foot syndrome,hypercholesterolemia,hoarseness,etc.,which were improved after symptomatic treatment and well tolerated by the patients.Conclusion After the failure of first-line targeted therapy,sequential combination of axitinib and tislelizumab in the treatment of advanced renal cell carcinoma has significant effect,i

关 键 词：阿昔替尼 替雷利珠单抗 靶向治疗 晚期肾癌 

分 类 号：R979.1[医药卫生—药品]