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Peng Linhui, Chen Tao, Xu Yunxiuxiu, et al. Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus[J]. Chinese Journal of Digestive Surgery, 2024, 23(2): 265-271. DOI: 10.3760/cma.j.cn115610-20240126-00044
Citation: Peng Linhui, Chen Tao, Xu Yunxiuxiu, et al. Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus[J]. Chinese Journal of Digestive Surgery, 2024, 23(2): 265-271. DOI: 10.3760/cma.j.cn115610-20240126-00044
shu

Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus

  • 1.

    Department of Hepatobiliary Surgery, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou510120, China

  • 2.

    Department of Radiology, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou510120, China

Funds: 

Talent Exchange Service Center of National Health Commission RCLX2315049

Guangdong Provincial Clinical Research Center for Digestive Diseases 2020B 1111170004

More Information
  • Corresponding author:

    Chen Yajin, Email: cyj0509@126.com

  • Received Date: January 25, 2024
  • Available Online: June 23, 2024
    Graphical Abstract
    • Abstract
  • Objective 

    To investigate the efficacy of mFOLFOX7 regimen systemic chemo⁃therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).

    Methods 

    The single‑arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages.

    Results 

    (1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment‑associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow‑up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow‑up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow‑up (3 cases completed treatment and entered follow‑up observation). The longest survival time was 31.0 months.

    Conclusion 

    The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

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    • References (39)
  • [1]
    ShuqunC, MengchaoW, HanC, et al. Tumor thrombus types influence the prognosis of hepatocellular carcinoma with the tumor thrombi in the portal vein[J]. Hepatogastroenterology,2007,54(74):499‑502.
    [2]
    JiangJF, LaoYC, YuanBH, et al. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges[J]. Oncotarget,2017,8(20):33911‑33921. DOI: 10.18632/oncotarget.15411.
    [3]
    European Association for the Study of the Liver. EASL clini⁃cal practice guidelines: management of hepatocellular car⁃cinoma[J]. J Hepatol,2018,69(1):182‐236. DOI:10.1016/j.jhep. 2018.03.019.
    [4]
    BrederVV, VogelA, MerleP, et al. IMbrave150: exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients (pts) with main trunk and/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo)+bevacizumab (bev) versus sorafenib (sor) in a global Ph Ⅲ study [J]. J Clin Oncol,2021,39(15_suppl):4073.
    [5]
    中国医师协会肝癌专业委员会.中国肝细胞癌合并门静脉癌栓诊疗指南(2021年版)[J].中华医学杂志,2022,102(4):243‑254.DOI: 10.3760/cma.j.cn112137-20211117-025677.
    [6]
    《原发性肝癌诊疗规范(2019年版)》编写专家委员会.原发性肝癌诊疗规范(2019年版)[J].中国临床医学,2020,27(1):140-156. DOI: 10.12025/j.issn.1008-6358.2020.20200065.
    [7]
    LiXP, WenF, YangW, et al. The role of tiopronin for the prevention of chemotherapy‑related liver toxicity in advan-ced colorectal cancer patients treated with mFOLFOX7: a prospective analysis[J]. Tumori,2014,100(4):446‑451. DOI: 10.1700/1636.17908.
    [8]
    XuJ, ZhangY, JiaR, et al. Anti‑PD‑1 antibody SHR‑1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open‑label, dose escalation and expansion study[J]. Clin Cancer Res,2019,25(2):515‑523. DOI:10.1158/1078-0432. CCR-18-2484.
    [9]
    LencioniR, LlovetJM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma[J]. Semin Liver Dis,2010,30(1):52‑60. DOI: 10.1055/s-0030-1247132.
    [10]
    张浩,仲富瑞,程宦立,等.肝动脉灌注化疗栓塞联合射频消融治疗中晚期肝癌的疗效分析[J].中国普通外科杂志,2020,29(1):35‑42. DOI: 10.7659/j.issn.1005-6947.2020.01.005.
    [11]
    GonH, KidoM, TanakaM, et al. Growth velocity of the portal vein tumor thrombus accelerated by its progression, alpha‑fetoprotein level, and liver fibrosis stage in patients with hepatocellular carcinoma[J]. Surgery,2018,164(5):1014‑1022. DOI: 10.1016/j.surg.2018.06.025.
    [12]
    翟伟,曹李,许世友,等.原发性肝细胞癌合并门静脉癌栓手术治疗的预后相关因素分析[J/CD].中华普外科手术学杂志:电子版,2022,16(6):610‑613. DOI:10.3877/cma.j.issn. 1674-3946.2022.06.008.
    [13]
    WangK, GuoWX, ChenMS, et al. Multimodality treatment for hepatocellular carcinoma with portal vein tumor throm-bus: a large‑scale, multicenter, propensity mathching score analysis[J]. Medicine (Baltimore),2016,95(11):e3015. DOI: 10.1097/MD.0000000000003015.
    [14]
    LiXL, GuoWX, HongXD, et al. Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score analysis[J]. Hepatol Res,2016,46(11):1088‑1098. DOI: 10.1111/hepr.12657.
    [15]
    ShuiY, YuW, RenX, et al. Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis[J]. Radiat Oncol,2018,13(1):188. DOI: 10.1186/s13014-018-1136-5.
    [16]
    苏茂,周军,王喆,等.125I粒子植入治疗肝细胞癌合并门静脉癌栓的初步临床疗效分析[J].中华转移性肿瘤杂志,2023,6(1):19‑24. DOI: 10.3760/cma.j.cn101548-20210927-00110.
    [17]
    蒋富强,杜鹏,张嘉诚.FOLFOX4方案肝动脉灌注化疗联合 125I粒子植入治疗原发性肝癌合并Ⅲ型门静脉癌栓患者的疗效与安全性研究[J].中国医师进修杂志,2022,45(5):415-421.DOI: 10.3760/cma.j.cn115455-20210908-01131.
    [18]
    曹白露,艾敏,黄平,等.中晚期肝细胞癌的局部治疗联合系统治疗研究进展[J].临床肝胆病杂志,2023,39(8):1972-1976. DOI: 10.3969/j.issn.1001-5256.2023.08.031.
    [19]
    戴文聪,臧梦雅,袁国盛,等.肝动脉灌注化疗及其综合治疗方案对中晚期肝细胞癌患者的临床疗效及预后因素分析[J].临床肝胆病杂志,2023,39(7):1592-1599. DOI: 10.3969/j.issn.1001-5256.2023.07.013.
    [20]
    赵增富,王茹芳,任庆莹,等.肝动脉化疗栓塞联合射频消融治疗肝癌合并门静脉癌栓的疗效分析[J].中国现代普通外科进展,2014,17(8):634-636. DOI: 10.3969/j.issn.1009-9905.2014.08.017.
    [21]
    GallePR, FinnRS, QinS, et al. Patient‑reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave 150): an open‑label, randomised, phase 3 trial[J]. Lancet Oncol,2021,22(7):991‑1001. DOI: 10.1016/S1470-2045(21)00151-0.
    [22]
    RenZ, XuJ, BaiY, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepa-tocellular carcinoma (ORIENT‑32): a randomised, open-label, phase 2‑3 study[J]. Lancet Oncol,2021,22(7):977‑990. DOI: 10.1016/S1470-2045(21)00252-7.
    [23]
    KudoM, IkedaM, MotomuraK, et al. A phase Ⅰb study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): study 117[J]. J Clin Oncol,2020,38(4_suppl):513. DOI: 10.1200/JCO.2020.38.4_suppl.513.
    [24]
    LlovetJM, KudoM, MerleP, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepa-tocellular carcinoma (LEAP‑002): a randomised, double-blind, phase 3 trial[J]. Lancet Oncol,2023,24(12):1399-1410. DOI: 10.1016/S1470-2045(23)00469-2.
    [25]
    QinS, ChanSL, GuS, et al. Camrelizumab plus rivoceranib versus sorafenib as first‑line therapy for unresectable hepa-tocellular carcinoma (CARES‑310): a randomised, open-label, international phase 3 study[J]. Lancet,2023,402(10408):1133‑1146.DOI: 10.1016/S0140-6736(23)00961-3.
    [26]
    樊嘉,高强.肝癌的免疫治疗:有希望便是光明[J].中华消化外科杂志,2022,21(2):199‑204. DOI:10.3760/cma.j.cn11 5610-20220215-00080.
    [27]
    QinS, BaiY, LimHY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia[J]. J Clin Oncol,2013,31(28):3501‑3508. DOI:10.1200/JCO.2012.44. 5643.
    [28]
    QinS, ChengY, LiangJ, et al. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup ana-lysis of the EACH study[J]. Oncologist,2014,19(11):1169-1178. DOI: 10.1634/theoncologist.2014-0190.
    [29]
    LyuN, KongY, MuL, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma[J]. J Hepatol,2018,69(1):60‑69. DOI: 10.1016/j.jhep.2018.02.008.
    [30]
    HeM, LeY, LiQ, et al.使用mFOLFOX进行肝动脉灌注化疗与肝动脉化疗栓塞术治疗不可切除的巨块型肝细胞癌:一项前瞻性非随机研究[J].癌症,2018,37(6):251-259.
    [31]
    YanJingxin, DengManjun, TingLi, et al.Efficacy and complications of transarterial chemoembolization alone or in combination with different protocols for hepatocellular carcinoma: a Bayesian network meta‑analysis of randomized controlled trials[J].iLIVER,2023, 2(2): 130‑141. DOI: 10.1016/j.iliver.2023.03.002.
    [32]
    HeMK, ShiM, LaiZC, et al. A phase Ⅱ trial of lenvatinib plus toripalimab and hepatic arterial infusion chemotherapy as a first‐line treatment for advanced hepatocellular carcinoma (LTHAIC study)[J]. J Clin Oncol,2021,39(15_ suppl):4083. DOI: 10.1200/JCO.2021.39.15_suppl.4083.
    [33]
    刘东明,穆瀚,刘长富,等.免疫及靶向药物联合肝动脉灌注化疗治疗晚期肝癌的回顾性分析[J].中国肿瘤临床,2023,50(17):888‑892. DOI:10.12354/j.issn.1000-8179.2023.202 30764.
    [34]
    ZhangTQ, ZuoMX, GengZJ, et al. Hepatic artery infusion chemotherapy (HAIC) combined with apatinib and camre-lizumab for hepatocellular carcinoma (HCC) in BCLC stage C: a prospective, single‑arm, phase Ⅱ trial (TRIPLET study)[J]. Ann Oncol,2021,32(Suppl 5):S825.
    [35]
    徐永康,付舒敏,李丹,等.肝动脉灌注化疗联合卡瑞利珠单抗和仑伐替尼治疗肝癌合并VP3/4型门静脉癌栓的近期疗效与安全性[J].南昌大学学报:医学版,2022,62(5):32-37. DOI: 10.13764/j.cnki.ncdm.2022.05.006.
    [36]
    XuYK, FuSM, MaoY, et al. Hepatic arterial infusion chemo-therapy (HAIC) combined with tislelizumab and lenvatinib for advanced hepatocellular carcinoma (aHCC) with Vp3‑4 portal vein tumor thrombosis (PVTT): a single‑arm, phase Ⅱ study[J]. J Clin Oncol,2023,41(16_suppl):e1645. DOI: 10.1200/JCO.2023.41.16_suppl.e16166.
    [37]
    程树群,孙居仙.肝癌合并门静脉癌栓的诊治进展[J].中国普外基础与临床杂志,2019,26(5):513-518. DOI: 10.7507/1007-9424.201904022.
    [38]
    刘潇衍.肿瘤化疗联合免疫治疗从理论基础到临床实践[J].中国肿瘤临床,2017,44(9):452‑458. DOI:10.3969/j.issn. 1000-8179.2017.09.177.
    [39]
    ZhuH, ShanY, GeK, et al. Oxaliplatin induces immunogenic cell death in hepatocellular carcinoma cells and synergizes with immune checkpoint blockade therapy[J]. Cell Oncol (Dordr),2020,43(6):1203‑1214. DOI:10.1007/s134 02-020-00552-2.
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