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中华介入放射学电子杂志 ›› 2021, Vol. 09 ›› Issue (02) : 127 -134. doi: 10.3877/cma.j.issn.2095-5782.2021.02.002

所属专题: 文献

肿瘤介入

DEB-TACE联合仑伐替尼治疗晚期肝细胞癌的疗效和安全性
傅云霞1, 徐梓宁1, 黄敬君1, 郭永建1, 黄文薮1, 朱康顺1,()   
  1. 1. 510260 广东广州,广州医科大学附属第二医院微创介入科
  • 收稿日期:2021-02-04 出版日期:2021-05-25
  • 通信作者: 朱康顺
  • 基金资助:
    国家自然科学基金(82001930、81873920); 广东省医学科学技术研究基金(B2019055); 广州市科技计划项目(202002030135)

The efficacy and safety of drug-eluting bead transarterial chemoembolization combined with lenvatinib in patients with advanced hepatocellular carcinoma

Yunxia Fu1, Zining Xu1, Jingjun Huang1, Yongjian Guo1, Wensou Huang1, Kangshun Zhu1,()   

  1. 1. Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangdong Guangzhou 510260, China
  • Received:2021-02-04 Published:2021-05-25
  • Corresponding author: Kangshun Zhu
引用本文:

傅云霞, 徐梓宁, 黄敬君, 郭永建, 黄文薮, 朱康顺. DEB-TACE联合仑伐替尼治疗晚期肝细胞癌的疗效和安全性[J/OL]. 中华介入放射学电子杂志, 2021, 09(02): 127-134.

Yunxia Fu, Zining Xu, Jingjun Huang, Yongjian Guo, Wensou Huang, Kangshun Zhu. The efficacy and safety of drug-eluting bead transarterial chemoembolization combined with lenvatinib in patients with advanced hepatocellular carcinoma[J/OL]. Chinese Journal of Interventional Radiology(Electronic Edition), 2021, 09(02): 127-134.

目的

评价载药微球经肝动脉化疗栓塞术(DEB-TACE)联合仑伐替尼治疗晚期肝细胞(HCC)的疗效和安全性。

方法

回顾性评价2018年11月至2019年12月期间在我科接受DEB-TACE联合仑伐替尼治疗的不可切除晚期HCC患者的病例资料。仑伐替尼在DEB-TACE后3~5 d口服给药(体重大于60 kg,12 mg/d;体重小于60 kg,8 mg/d)。我们评估了不良事件(AEs)发生率、客观缓解率(ORR)、疾病控制率(DCR)、无疾病进展生存期(PFS)和生存率(OS)等。对OS进行生存分析,采用多因素Cox比例风险回归模型确定OS的独立影响因素。

结果

本研究纳入符合研究条件的43例患者,Child-Pugh分级A级28例(65.1%),B级15例(34.9%)。中位随访时间为13.0个月(3.0~27.0个月),平均接受2.6次(2~4次)DEB-TACE,仑伐替尼的中位给药时间为12.5个月(3.0~27.0个月)。随访过程中,19例患者(44.2%)发生了与TACE相关的不良事件,其中3级不良事件1例(2.3%)。39例患者(90.7%)发生了与仑伐替尼相关的不良事件,其中13例(30.2%)发生3级不良事件。该13例中,5例患者经对症治疗不良反应缓解,仑伐替尼恢复原剂量,7例通过剂量减量不良反应缓解,1例患者接受了终身停药。DEB-TACE联合仑伐替尼治疗ORR和DCR分别为69.7%和88.4%,中位PFS为7.0个月(95%CI:5.4~8.6个月),OS为15.0个月(95%CI:11.3~18.7个月)。在单变量和多变量分析中,腹水(HR = 2.890,95%CI:1.018~8.199;P = 0.046)和肝外转移(HR = 2.267,95%CI:1.044~4.923;P = 0.039)是OS的独立预后因素。

结论

DEB-TACE联合仑伐替尼治疗晚期肝癌是安全的,腹水和肝外转移是影响患者生存期的预后因素。

Objective

To evaluate the safety and effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with lenvatinib in patients with unresectable advanced hepatocellular carcinoma (HCC).

Methods

This study prospectively collected and retrospectively evaluated medical records from patients with unresectable advanced HCC who underwent DEB-TACE-lenvatinib from November 2018 to December 2019. Lenvatinib (12 mg/day or 8 mg/day for bodyweight ≥60 or < 60 kg, respectively) was initiated 3~5 days after DEB-TACE. We evaluated safety, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS).

Results

Forty-three patients with advanced HCC underwent treatment with DEB-TACE-lenvatinib were included in this study; 65.1%(28/43) were Child-Pugh class A and 34.9%(15/43) were Child-Pugh class B. The median follow-up time was 13.0 months (3.0~27.0 months). Patients received an average of 2.6 DEB-TACE ( 2 to 4 times); Median duration of administration of lenvatinib was 12.5 months (3.0 to 27.0 months). TACE-related adverse events (AEs) occurred in 44.2%(19/43) of patients; only one patient developed a grade 3 AE. Lenvatinib-related AEs of any grade occurred in 90.7%(39/43), and Grade 3 in 30.2%(13/43). Among 13 patients with Grade 3 AEs, 12 experienced treatment interruption followed by resumed treatment either at the same dose (n = 5; 11.6%) or at a reduced dose (n = 7; 16.3%), one patient experienced discontinued lenvatinib treatment. The ORR and DCR for DEB-TACE-lenvatinib were 69.7% and 88.4%, respectively. The median PFS and OS were 7.0 months (95%CI: 5.4~8.6 months) and 15.0 months (95%CI: 11.3~18.7 months), respectively. Presence of ascites (HR = 2.890, 95%CI: 1.018~8.199; P = 0.046) and extrahepatic metastasis (HR = 2.267, 95%CI: 1.044~4.923; P = 0.039) were the independent prognostic factors for OS.

Conclusions

The combination of DEB-TACE and lenvatinib was safe and effective in patients with advanced HCC.

表1 患者的基线特征[n(%)]
图1 患者流程图
表2 与DEB-TACE相关的不良事件(n = 43)
表3 与仑伐替尼相关的不良事件(n = 43)
表4 DEB-TACE联合仑伐替尼治疗晚期肝细胞癌的治疗效果
图2 DEB-TACE联合仑伐替尼治疗晚期肝细胞癌患者的无进展生存期(PFS)Kaplan-Meier曲线
图3 DEB-TACE联合仑伐替尼治疗晚期肝细胞癌患者的总生存(OS)Kaplan-Meier曲线
表5 OS预后因素的单变量分析
影响因素 病例数(n = 43) 中位OS(月)(95%CI Pa
性别     0.806
  39 15.0(10.3, 19.7)  
  4 12.0(6.0, 18.0)  
年龄(岁)     0.649
  < 60 32 15.0(10.5, 19.5)  
  ≥ 60 11 12.0(7.7, 16.3)  
体力状况评分     0.169
  0 34 14.0(9.2, 18.8)  
  1 9 15.0(7.1, 22.9)  
Child-Pugh分级     0.245
  A 28 17.0(11.6, 22.4)  
  B 15 12.0(6.7, 17.3)  
腹水     0.023
  6 8.0(4.2, 11.8)  
  37 15.0(11.9, 18.0)  
肝病病因     0.643
  乙肝 40 15.0(10.8, 19.2)  
  非乙肝 3 14.0(9.2, 18.8)  
大血管侵犯     0.175
  28 14.0(8.7, 19.3)  
  15 15.0(6.3, 23.7)  
肿瘤大小(cm)     0.876
  < 5 17 17.0(9.5, 24.5)  
  ≥ 5 26 14.0(9.5, 18.5)  
肿瘤个数     0.580
  1~3 9 14.0(5.2, 22.8)  
  > 3 34 15.0(10.4, 19.6)  
肝外转移     0.023
  20 10.0(7.8, 12.2)  
  23 18.0(14.6, 21.4)  
甲胎蛋白(ng/mL)     0.062
  < 400 22 17.0(10.3, 23.7)  
  ≥ 400 21 14.0(8.4, 19.6)  
血清总胆红素(μmol/L)     0.534
  < 23 33 15.0(12.1, 17.8)  
  ≥23 10 12.0(9.1, 14.9)  
血清白蛋白(g/dL)     0.435
  < 35 18 14.0(10.5, 17.5)  
  ≥35 25 15.0(6.4, 23.6)  
凝血酶原时间(s)     0.173
  ≤13 22 18.0(9.0, 27.0)  
  > 13 21 14.0(9.2, 18.8)  
血小板计数(109/L)     0.496
  < 125 13 11.0(7.8, 14.2)  
  ≥125 30 15.0(11.7, 18.3)  
肝切除或消融病史     0.902
  8 9.0(0, 21.0)  
  35 15.0(11.5, 18.5)  
与仑伐替尼相关3级不良事件     0.756
  13 11.0(4.4, 17.7)  
  30 15.0(11.7, 18.3)  
表6 OS预后因素的多变量分析
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