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*

doi:10.3969/j.issn.1672-5069.2025.03.027

摘要/Abstract

摘要： 目的探讨FOLFOX 肝动脉灌注化疗(HAIC)联合仑伐替尼和程序性细胞死亡受体-1(PD-1抑制剂治疗中晚期原发性肝癌(PLC)患者的疗效。方法 2020年1月～2022年12月我院收治的中晚期PLC患者86例,被随机分为对照组43例和观察组43例,两组均接受经 HAIC 化疗FOLFOX 方案和仑伐替尼治疗,观察组在此基础上应用信迪利单抗,21 d为1个周期,两组均连续治疗4个周期。随访2年。使用Quanteon流式细胞仪检测外周血T淋巴细胞亚群,采用ELISA法检测血清癌抗原 199()、甲胎蛋白(AFP)和癌胚抗原(CEA)水平。结果观察组完全缓解率和部分缓解率分别11.6%和74.4%,总有效率为86.1%,显著高于对照组的4.7%、60.5%和65.1%(P＜0.05);治疗后,观察组外周血CD3⁺和CD4⁺细胞百分比分别为(46.9±5.3)%和(40.4±5.2)%,均显著高于对照组【分别为(40.4±4.8)%和(34.1±4.3)%,P＜0.05】,而CD8⁺细胞百分比为(16.1±2.4)%,显著低于对照组【(22.3±3.5)%, P＜0.05);观察组血清甲胎蛋白水平为(102.6±11.2)ng/mL,显著低于对照组【(143.0±15.4)ng/mL,P＜0.05】;观察组血清ALT和AST水平分别为(49.0±4.0)U/L和(44.4±5.0)U/L,均显著高于对照组【分别为(41.8±4.8)U/L和(38.2±5.3)U/L,P＜0.05】;在随访2年末,观察组生存率为67.4%,无疾病进展生存时间为(16.2±2.8)个月,显著高于对照组【分别为39.5%和(11.8±3.2)个月,P＜0.05】。结论采用HAIC 化疗FOLFOX方案与仑伐替尼和信迪利单抗联合治疗中晚期PLC患者可以提高短期肿瘤缓解率,延长生存时间。

关键词: 原发性肝癌, FOLFOX方案, 肝动脉灌注化疗, 仑伐替尼, 信迪利单抗, 治疗

Abstract: Objective The aim of this study was to investigate therapeutic efficacy of FOLFOX in hepatic artery infusion chemotherapy (HAIC) with combination of lenvatinib and PD-1 inhibitors in treatment of patients with advanced primary liver cancer(PLC). Methods 86 patients with advanced, unresectable PLC were encountered in our hospital between January 2020 and December 2022, and were randomly assigned to receive FOLFOX through HAIC chemotherapy plus lenvatinib in 43 patients (control), or to receive sintilimab at base of regimen mentioned above in another 43 patients (observation) for three months, and followed-up for two years. Peripheral blood lymphocyte subsets were detected by FCM, and serum alpha-fetoprotein (AFP) level was assayed by ELISA. Results Complete remission rate and partial remission rate in the observation group were 11.6% and 74.4%, with total effective rate of 86.1%, both significantly higher than 4.7% and 60.5%, with total effective rate of 65.1%(P＜0.05) in the control; after treatment, percentages of peripheral blood CD3⁺ and CD4⁺ cells were (46.9±5.3)% and (40.4±5.2)%, both much higher than [(40.4±4.8)% and (34.1±4.3)%, respectively, P＜0.05], while percentage of CD8⁺ cells was (16.1±2.4)%, much lower than [(22.3±3.5)%, P＜0.05) in the control; serum AFP level was (102.6±11.2)ng/mL, much lower than [(143.0±15.4)ng/mL, P＜0.05]in the control group; serum ALT and AST levels were (49.0±4.0)U/L and (44.4±5.0)U/L, both much higher than [(41.8±4.8)U/L and (38.2±5.3)U/L, respectively, P＜0.05]in the control; by end of two-year follow-up, the survival rate in the observation group was 67.4%, with progression-free survival (PFS) of (16.2±2.8)m, significantly higher than 39.5%, with PFS of (11.8±3.2)m in the control (P＜0.05). Conclusion The combination of FOLFOX through HAIC and Lenvatinib plus sintilimab in dealing with patients with advanced PLC could elevate short-term remission rate and prolong survival, and warrants further clinical investigation.

Key words: Hepatoma, FOLFOX regimen, Hepatic artery infusion chemotherapy, Lenvatinib, Sintilimab monoclonal antibody, Therapy

杨懿瑾, 洪晗, 陈彬, 崔洪全, 王逸, 张甲. 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.

Yang Yijin, Hong Han, Chen Bin, et al. FOLFOX in hepatic artery infusion chemotherapy with combination of lenvatinib and PD-1 inhibitors in treatment of patients with advanced primary liver cancer[J]. Journal of Practical Hepatology, 2025, 28(3): 426-429.

参考文献

[1] Zhou H, Song T. Conversion therapy and maintenance therapy for primary hepatocellular carcinoma. Biosci Trends, 2021,15(3):155-160.
[2] France NL, Blair HA. Tremelimumab: a review in advanced or unresectable hepatocellular carcinoma. Target Oncol, 2024, 19(1):115-123.
[3] Zhang B, Huang B, Yang F, et al. High-risk hepatocellular carcinoma: hepaticarterial infusion chemotherapy versus transarterial chemoembolization. J Hepatocell Carcinoma, 2024,11:651-663.
[4] Zhang Y, Qin S, Chao J,et al. The in-vitro antitumor effects of AST-3424 monotherapy and combination therapy with oxaliplatin or 5-fluorouracil in primary liver cancer. Front Oncol, 2022,12:885139.
[5] Ventura C, Junco M, Santiago Valtierra FX,et al. Synergism of small molecules targeting VDAC with sorafenib, regorafenib or lenvatinib on hepatocarcinoma cell proliferation and survival. Eur J Pharmacol, 2023, 957:176034.
[6] Villacampa G, Cresta Morgado P, Navarro V,et al. Comprehensive evaluation of surrogate endpoints to predict overall survival in trials with PD1/PD-L1 immune checkpoint inhibitors plus chemotherapy. Cancer Treat Rev, 2023, 116:102542.
[7] Diao L, Wang C, You R,et al. Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors versus lenvatinib and PD-1 inhibitors for HCC refractory to TACE. J Gastroenterol Hepatol, 2024, 39(4):746-753.
[8] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019 年版). 中华肝脏病杂志, 2020, 28(2):112-128.
[9] Jiang X, Aljbri A, Liu J,et al. Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report. Front Oncol, 2024, 14:1401882.
[10] Liang RB, Zhao Y, He MK,et al. Hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin with or without sorafenib as initial treatment for advanced hepatocellular carcinoma. Front Oncol, 2021, 11:619461.
[11] Mei J, Yu H,Qin L,et al. FOLFOX-HAIC for unresectable large hepatocellular carcinoma: the effectiveness has yet to be determined. J Clin Oncol, 2022, 40(16):1841.
[12] Liu BJ, Gao S, Zhu X,et al. Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors for advanced hepatocellular carcinoma. Immunotherapy, 2021, 13(17):1395-1405.
[13] Nathan J, Shameera R, Palanivel G. Studying molecular signaling in major angiogenic diseases. Mol Cell Biochem, 2022, 477(10):2433-2450.
[14] Filippone A, Lanza M, Mannino D, et al. PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression. Cancer Immunol Immunother, 2022, 71(9):2067-2075.
[15] Glorieux C, Cui L, Zeng P,et al. Diverse effects ofchemotherapeutic agents on immune cell function and implications in immunochemotherapy. Cancer Commun (Lond), 2021, 41(5):432-435.
[16] Iesato A, Li S, Sadow PM,et al. The tyrosine kinase inhibitor lenvatinib inhibits anaplastic thyroid carcinoma growth bytargeting pericytes in the tumor microenvironment. Thyroid, 2023, 33(7):835-848.
[17] Zhong SJ, Liu X, Kaneko T,et al. Peptide blockers of PD-1-PD-L1 interaction reinvigorate PD-1-Suppressed T cells and curb tumor growth in mice. Cells, 2024, 13(14):1193.
[18] Li M, Liao J, Wang L,et al. A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy. Front Immunol, 2024, 15:1303259.
[19] 刘禹辰,朱建交,陶计林,等. 肝动脉灌注化疗联合仑伐替尼、卡瑞利珠单抗治疗不可切除肝癌的临床观察. 中国药物应用与监测,2023,20(4):221-225.
[20] Yin J, Wu Y, Yang X,et al. Checkpoint inhibitor pneumonitis induced by anti-PD-1/PD-L1 therapy in non-small-cell lung cancer: occurrence and mechanism. Front Immunol, 2022, 13:830631.

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^*

FOLFOX in hepatic artery infusion chemotherapy with combination of lenvatinib and PD-1 inhibitors in treatment of patients with advanced primary liver cancer

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