临床外科杂志 ›› 2024, Vol. 32 ›› Issue (2): 176-181.doi: 10.3969/j.issn.1005-6483.2024.02.015

• 论著 • 上一篇    下一篇

经肝动脉化疗栓塞联合酪氨酸激酶抑制剂及程序性死亡受体-1抗体治疗中晚期不可切除肝细胞癌的临床疗效和安全性分析

  

  1. 637000  四川南充,川北医学院附属医院肝胆外一科,川北医学院肝胆胰肠疾病研究所
  • 收稿日期:2023-02-19 修回日期:2023-02-19 接受日期:2023-02-19 出版日期:2024-02-20 发布日期:2023-02-20
  • 通讯作者: 武国,Email:cqxnyywg@163.com

Efficacy and safety of transhepatic arterial chemoembolization combined with tyrosine kinase inhibitor and programmed death receptor-1 inhibitors in the treatment of  intermediate and a-dvanced unresectable hepatocellular carcinoma

  1. Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College,Institute of Hepatobiliary-Pancreatic-Intestinal of North Sichuan Medical College,Nanchong,Sichuan 637000,China
  • Received:2023-02-19 Revised:2023-02-19 Accepted:2023-02-19 Online:2024-02-20 Published:2023-02-20

摘要: 目的 探讨经肝动脉化疗栓塞术(TACE)联合酪氨酸激酶抑制剂(TKIs)及程序性死亡受体-1(PD-1)抑制剂治疗中晚期不可切除肝细胞癌(以下简称肝癌)的临床效果。方法 2020年1月~2022年1月我院收治的中晚期不可切除肝癌病人65例,均采用TACE+TKIs+PD-1抗体治疗。观察肿瘤反应、客观缓解率、疾病控制率、总生存时间、无进展生存时间、转化手术率和药物不良反应等。结果 65例病人的客观缓解率为49.2%(32/65),疾病控制率为89.2%(58/65),其中完全缓解2例,部分缓解30例,疾病稳定26例,疾病进展7例。65例病人中,18例转化为可切除肝癌,行R0手术切除,转化手术率为27.6%(18/65)。65例病人均获得随访,随访时间3~22.4个月,中位随访时间16.5个月。65例病人中位总体生存时间、中位疾病无进展生存时间分别为14.5个月(95%CI为12.3~16.6个月)、8.8个月(95%CI为6.9~10.6个月)。65例病人治疗后均出现栓塞后综合征(腹痛、发热、恶心、呕吐等症状),部分病人出现短暂的肝功能异常。3级以下药物不良反应均在1周内恢复。部分病人合并多种药物不良反应。其中1例(1.5%)因顽固性呕吐停用TACE治疗,5例因治疗过程中严重肝功能损伤停用仑伐替尼,2例因严重反应性毛细血管增生停用卡瑞利珠单抗,1例因严重甲状腺功能减退停用替雷利珠单抗,1例因顽固消化道出血停用仑伐替尼及信迪利单抗。其他治疗病人发生3~4级药物不良反应经药物减量及对症处理后均缓解。结论 TACE+TKIs+PD-1抗体治疗中晚期不可切除肝癌可靠、安全。

关键词: 肝细胞癌, 经动脉化疗栓塞, 酪氨酸激酶抑制剂, 程序性死亡受体-1抑制剂, 临床疗效

Abstract: Objective To investigate the clinical effect of transhepatic arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and programmed death receptors-1 (PD-1) inhibitors (TACE+TKIs+PD-1 antibody) in the treatment of moderate advanced unresectable hepatocellular carcinoma (HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate (ORR),disease control rate (DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 patients with hepatocellular carcinoma was 49.2% (32/65),and the DCR was 89.2% (58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6% (18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months (95% CI:12.3~16.6 months) and 8.8 months (95% CI:6.9~10.6 months),respectively.After treatment,65 patients all had post embolism syndrome (abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient (1.5%)  stopped using TACE because of stubborn vomiting,and 5 patients (7.6%) stopped using Lenvatinib because of severe liver function damage during treatment,2 patients (3%) stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient (1.5%) stopped using Tislelizumab because of severe hypothyroidism,one patient (1.5%) stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3~4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

Key words: hepatocellular carcinoma, transcatheter arterial chemoembolization, tyrosine kinase inhibitor, programmed death receptor-1 inhibitor, clinical efficacy

[1] 瞿伟峰 史颖弘 樊嘉. 美国国立综合癌症网络临床实践指南:肝细胞癌(2023.V2)更新解读[J]. 临床外科杂志, 2024, 32(1): 6-9.
[2] 朱新新 骆建军 王晓霞 蒋光伟 王黎鹏 郭起峰 孟威 邹春喜 杨箬箬 吴舒沁 吴倩. 床旁纤维支气管镜治疗对创伤性颅脑损伤合并肺部感染机械通气病人的临床影响[J]. 临床外科杂志, 2023, 31(9): 826-829.
[3] 胡家瑞 宋明 余来. 经皮微创与开放手术治疗胸腰椎骨折的疗效及安全性分析[J]. 临床外科杂志, 2023, 31(9): 881-884.
[4] 慕喜喜 李静 张玄 高小鹏 刘保荣 钟岳. miR-3619-5p、LINC00857在原发性肝细胞癌血清中表达水平及其临床诊断价值分析[J]. 临床外科杂志, 2023, 31(6): 572-575.
[5] 刘金玮 巴林超 张劲夫 范正军. 低氧脂滴诱导相关蛋白在肝细胞癌中的表达情况及临床意义[J]. 临床外科杂志, 2023, 31(5): 447-452.
[6] 严凤翔. 辅助TriGen交锁髓内钉联合肩外展架治疗肱骨近端骨折临床疗效观察[J]. 临床外科杂志, 2023, 31(4): 330-333.
[7] 徐仁良 沈松柏 余龙伍 华双一 吴扬 徐标 李春. 载药微球经动脉化疗栓塞与传统肝动脉化疗栓塞分别联合索拉非尼治疗中晚期肝细胞肝癌的有效性和安全性对比[J]. 临床外科杂志, 2023, 31(4): 383-386.
[8] 张松 杨璞 时宏富 胡海清 徐海军. 开放楔形胫骨高位截骨术治疗内翻膝骨关节炎的疗效观察及治疗体验[J]. 临床外科杂志, 2023, 31(3): 286-289.
[9] 熊坚威 武国 赵开烽 英保. 肝动脉化疗栓塞联合卡瑞利珠单抗成功转化不可切除肝癌一例[J]. 临床外科杂志, 2023, 31(2): 136-137.
[10] 林丽燕 董佳 肖伟进 彭然 吴方君 马辉 力超 刘景丰. 基于全偏振成像和机器学习的肝细胞癌与肝内胆管癌鉴别诊断研究[J]. 临床外科杂志, 2023, 31(2): 164-167.
[11] 武烨晔 王葵. 肝细胞癌的术后辅助治疗现状及展望[J]. 临床外科杂志, 2023, 31(10): 907-910.
[12] 徐剑军 顾劲扬. 新辅助免疫治疗在肝癌肝移植中的研究进展[J]. 临床外科杂志, 2023, 31(10): 911-915.
[13] 劳垚佳 程洁 林梦璐 张海平 奉佳辉 牟娟丽 黄凯 胡凡 林军. LIM激酶1对肝癌细胞增殖、迁移及血管形成能力的影响[J]. 临床外科杂志, 2023, 31(10): 920-924.
[14] 杜佳家 黄志勇. 肝细胞癌免疫治疗疗效预测的研究进展[J]. 临床外科杂志, 2023, 31(10): 990-993.
[15] 袁童 黄志勇. 肝癌免疫治疗4.0[J]. 临床外科杂志, 2022, 30(5): 490-493.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 栾杰. 当前国内乳房再造的几个原则与技术问题[J]. 临床外科杂志, 2020, 28(12): 1101 -1102 .
[2] 何雨竹, 倪鑫, 张潍平. 儿童先天性肾盂输尿管连接部梗阻性肾积水手术治疗策略研究进展[J]. 临床外科杂志, 2021, 29(6): 501 -504 .
[3] 马先桃 李师亮 严丽 朱章强 冯异 程才. 杂交技术在StanfordA型主动脉夹层的应用现状[J]. 临床外科杂志, 2021, 29(12): 1101 -1103 .
[4] 闵心平 夏军 朱铁源 胡知朋 李博文 徐鹏 王志维. 急性重症肺栓塞外科治疗八例[J]. 临床外科杂志, 2021, 29(12): 1132 -1134 .
[5] 李疆 曹英豪 邓胜和 蔡开琳. 胃下部癌No.6组淋巴结分拣特点和转移危险因素分析[J]. 临床外科杂志, 2022, 30(9): 830 -834 .
[6] 解东阳 张兵强 李韶山. 基于SEER数据库的壶腹周围癌预后预测模型的构建[J]. 临床外科杂志, 2023, 31(7): 659 -665 .
[7] 梁宾勇 陈孝平. 免疫治疗时代肝癌外科治疗的机遇与挑战[J]. 临床外科杂志, 2023, 31(10): 901 -903 .
[8] 魏萌萌 吕志坤 李国珍 胡雪艳 许倩倩 郭静 耿彪. 血清血管生成素样蛋白8、血管细胞黏附分子-1水平联合检测对颅内动脉瘤栓塞术后脑血管痉挛的预测价值[J]. 临床外科杂志, 2023, 31(12): 1133 -1136 .
[9] 方滢 叶哲伟 陈孝平. 科学技术对现代外科学发展的影响[J]. 临床外科杂志, 2024, 32(1): 1 -5 .
[10] 瞿伟峰 史颖弘 樊嘉. 美国国立综合癌症网络临床实践指南:肝细胞癌(2023.V2)更新解读[J]. 临床外科杂志, 2024, 32(1): 6 -9 .