载药微球经动脉化疗栓塞术联合仑伐替尼、PD-1单抗治疗大肝癌的疗效

摘要/Abstract

摘要： 目的观察载药微球经动脉化疗栓塞术(DEB-TACE)、程序性死亡因子-1(PD-1)联合仑伐替尼治疗大肝癌的疗效。方法回顾性分析南京医科大学附属逸夫医院2021年7月至2023年1月就诊的大肝癌患者85例的病历资料,根据治疗方法分为对照组(n=42)和观察组(n=43),对照组接受仑伐替尼联合DCB-TACE治疗,观察组在此基础上另给予PD-1单抗治疗。对比2组血清学指标、疗效、肝功能、肿瘤标志物、预后与不良反应。结果相比于对照组,观察组的客观缓解率、疾病控制率均更高(P<0.05)。观察组治疗后的丙氨酸氨基转移酶(ALT)(38.10±3.12)U/L、甲胎蛋白(AFP)(97.25±11.08)ng/mL、天冬氨酸氨基转移酶(AST)(39.02±3.18)U/L、糖类蛋白199(CA199)(172.03±18.29)U/mL、总胆红素(TBil)(20.13±1.78)μmol/L、α-L-岩藻糖苷酶(AFU)(34.27±4.26)U/L,比对照组低[分别为ALT(43.09±4.37)U/L、(149.20±18.31)ng/mL、(43.19±3.76)U/L、(217.14±22.68)U/mL、(23.07±2.43)μmol/L、(50.06±6.18)U/L](P<0.05)。相比于对照组,观察组的基质金属蛋白酶-9(MMP-9)与血管内皮生长因子(VEGF)更低(P<0.05),且2年存活率更高。2组不良反应总发生率比较差异无统计学意义(P>0.05)。结论 DEB-TACE联合仑伐替尼、PD-1单抗治疗大肝癌疗效确切,可降低肿瘤标志物水平,调节VEGF、MMP-9表达,改善肝功能,且安全性良好。

关键词: 仑伐替尼, 程序性死亡因子-1单抗, 大肝癌, 载药微球经动脉化疗栓塞术, 临床疗效, 不良反应

Abstract: Objective To observe the efficacy of drug eluting bead transarterial chemoembolization (DEB-TACE) combined with lenvastinib and programmed death factor-1 (PD-1) monoclonal antibody in the treatment of large liver cancer. Methods The medical records of 85 patients with large liver cancer treated in Sir Run Run Hospital, Nanjing Medical University Hospital from July 2021 to January 2023 were retrospectively analyzed. According to the treatment methods, they were divided into a control group (n=42) and an observation group (n=43). The control group received lenvatinib combined with DCB-TACE treatment. On this basis, the observation group was also given PD-1 monoclonal antibody treatment. The serological indicators, therapeutic effects, liver functions, tumor markers, prognosis and adverse reactions in these two groups of patients were compared. Results Compared with the control group, the objective response rate and disease control rate of the observation group were both higher (P<0.05). In the observation group after treatment, the levels of alanine aminotransferase (ALT) (38.10±3.12) U/L, alpha-fetoprotein (AFP) (97.25±11.08) ng/mL, aspartate aminotransferase (AST) (39.02±3.18) U/L, carbohydrate protein 199 (CA199) (172.03±18.29) U/mL, total bilirubin (TBil) (20.13±1.78) μmol/L, and α-L-fucoidase (AFU) (34.27±4.26) U/L were lower than those of (149.20±18.31) ng/mL, (43.19±3.76) U/L, (217.14±22.68) U/mL, (23.07±2.43) μmol/L, (50.06±6.18) U/L in the control group, respectively (P<0.05). Compared with the control group after treatment, the matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the observation group were lower (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). The 2-year survival rate of the observation group was higher when compared with the control group (P<0.05). Conclusion The combination therapies of DEB-TACE with lenvastinib and PD-1 monoclonal antibody has demonstrated definite efficacy in the treatment of advanced hepatocellular carcinoma. It can reduce the levels of serum tumor markers, down-regulate VEGF and MMP-9 expression, improve liver function, and has shown a good safety profile.

Key words: Lenvastinib, Programmed death factor-1 monoclonal antibody, Large liver cancer, Drug eluting bead transarterial chemoembolization, Clinical effect, Adverse reaction

刘勇, 李壮, 朱峰. 载药微球经动脉化疗栓塞术联合仑伐替尼、PD-1单抗治疗大肝癌的疗效[J]. 肝脏, 2025, 30(10): 1335-1339.

LIU Yong, LI Zhuang, ZHU Feng. The efficacy of drug eluting bead transarterial chemoembolization combined with lenvastinib and PD-1 monoclonal antibody in the treatment of large liver cancer[J]. Chinese Hepatolgy, 2025, 30(10): 1335-1339.

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参考文献

[1] Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022,77(6):1598-1606.
[2] Wang W, Lu K, Jiang X, et al. Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer[J]. J Exp Clin Cancer Res, 2023,42(1):142.
[3] 李晨,曹爱红. 载药微球经动脉化疗栓塞术联合阿帕替尼及PD-1单抗治疗中晚期肝癌的疗效及安全性分析[J]. 徐州医科大学学报,2023,43(6):404-409.
[4] 刘江勇,胡蓓,赵林,等. TACE联合或不联合仑伐替尼及PD-1抑制剂治疗不可切除肝癌的疗效及对供血动脉影响[J]. 临床放射学杂志,2023,42(4):665-671.
[5] 宋震,李园园,王文刚,等. TACE联合酪氨酸激酶抑制剂和卡瑞利珠单抗对中晚期肝癌的疗效与安全性[J]. 介入放射学杂志,2023,32(6):549-553.
[6] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版)[J]. 中华消化外科杂志,2022,21(2):143-168.
[7] Eisenhauer E A , Therasse P , Bogaerts J , et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2):228-247.
[8] Dueck A C, Mendoza T R, Mitchell S A, et al. Validity and reliability of the US national cancer institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE)[J]. JAMA Oncol, 2015, 1(8):1051-1059.
[9] Wang Y, Lin W, Huang G, et al. The therapeutic principle of combined clearing heat and resolving toxin plus TACE on primary liver cancer: a systematic review and meta-analysis[J]. J Ethnopharmacol, 2024,319(1):117072.
[10] Dang Z, Jiang L, Huang F. Effect of bevacizumab administered prior to transarterial chemoembolization on the therapeutic effects of lenvatinib given post-TACE in primary liver cancer patients[J]. Int J Clin Pharmacol Ther, 2023,61(10):423-429.
[11] Tong W U, Zhiyun Y, Yuying Y, et al. Effect of decoction of fuzheng jiedu xiaoji formula plus chemoembolization on primary liver cancer in patients[J]. J Tradit Chin Med, 2022,42(3):446-450.
[12] 苗颖,赵昌. DEB-TACE联合C-TACE治疗巨块型肝癌的近期疗效及安全性研究[J]. 中国临床新医学,2024,17(7):812-817.
[13] 梁雄,伍楚蓉,唐武兵,等. 介入治疗联合仑伐替尼及信迪利单抗治疗中晚期肝癌的近期疗效观察[J]. 现代肿瘤医学,2023,31(20):3812-3817.
[14] 杜佼佼,聂伟杰,陈引弟. 信迪利单抗联合仑伐替尼治疗中晚期原发性肝癌的疗效及对血清免疫球蛋白水平的影响[J]. 转化医学杂志,2025,14(1):223-227.
[15] 杨懿瑾,洪晗,陈彬,等. FOLFOX肝动脉灌注化疗联合仑伐替尼和PD-1抑制剂治疗中晚期原发性肝癌患者疗效研究[J]. 实用肝脏病杂志,2025,28(3):426-429.
[16] Shimose S, Kawaguchi T, Tanaka M, et al. Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: a multicenter cohort study using data mining analysis[J]. Oncol Lett, 2020,20(3):2257-2265.
[17] 李琪,颜敏,苏珂,等. TACE术联合TKI及PD-1单抗综合治疗进展期肝癌的临床疗效及安全性分析[J]. 临床和实验医学杂志,2023,22(17):1813-1817.
[18] 杨建奇,曹文淼,吴银霞,等. 卡瑞利珠单抗或信迪利单抗联合仑伐替尼治疗肝癌的效果及对肿瘤标志物的影响[J]. 肝脏,2022,27(10):1080-1083.
[19] 张力苹,刘喜娟,胡潇,等. 经动脉化疗栓塞续贯肝动脉灌注化疗联合TKI和PD-1单抗在晚期肝癌一线治疗中的疗效观察[J]. 南方医科大学学报,2024,44(9):1831-1838.
[20] 钱厚龙,李阳,朱翔,等. 卡瑞利珠单抗联合仑伐替尼治疗不可切除肝细胞癌的疗效和安全性[J]. 肝脏,2023,28(4):452-456.
[21] 彭珍,毛咏梅,郭亚楠,等. 柴胡蚤休汤对原发性肝癌患者血清MMP-9、VEGF、IGF-2水平及MSCT检查情况的影响研究[J]. 长春中医药大学学报,2022,38(4):409-412.
[22] 赵容,李静,严涵,等. 柴胡化积方对原发性肝癌TACE术后综合征外周血炎症因子及bFGF、MMP-9、VEGF水平的影响[J]. 湖南中医药大学学报,2023,43(12):2328-2334.
[23] 占新庆,朱宝宝,李楠. 卡瑞利珠单抗联合化疗对老年非小细胞肺癌患者血清CY211、MMP-9表达的影响[J]. 临床和实验医学杂志,2023,22(5):473-477.
[24] 赖奉庭,刘华强,蔡永广. 卡瑞利珠单抗联合仑伐替尼或贝伐珠单抗治疗肝癌的疗效分析[J]. 新医学,2023,54(6):437-441.