靶向药物治疗肝细胞癌的最新进展

樊永强; 董胜利

doi:10.3969/j.issn.1001-5256.2018.02.046

靶向药物治疗肝细胞癌的最新进展

DOI: 10.3969/j.issn.1001-5256.2018.02.046

山西医科大学第二临床医学院普外科

详细信息

中图分类号: R735.7
计量
- 文章访问数: 2237
- HTML全文浏览量: 14
- PDF下载量: 492
- 被引次数: 0
出版历程
- 出版日期: 2018-02-20

Recent advances in targeted drug therapy for hepatocellular carcinoma

Department of General Surgery, The Second Clinical Medical School of Shanxi Medical University

摘要

摘要:
靶向药物对于肝细胞癌的治疗效果在临床上已经被广泛证实。随着科学技术的发展,越来越多的靶向药物相继出现。近期,瑞格菲尼、ramucirumab等靶向药物在相应的临床实验中也表现出了相当的潜力。更多的二线候选药物,比如c-Met抑制剂tivantinib与cabozantinib、VEGFR-2抑制剂ramuciruma临床试验正在进行。总结了近几年靶向药物治疗肝细胞癌的试验数据及最新进展,为下一步临床试验及治疗提供参考意见。
- 癌,肝细胞 /
- 靶向药物 /
- 药物疗法 /
- 临床试验 /
- 综述
Abstract:
More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC) .With the development of science and technology, more and more targeted drugs have appeared.In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials.In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab.This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.
- carcinoma, hepatocellular /
- targeted drug /
- drug therapy /
- clinical trial /
- review

HTML全文

参考文献(35)

[1]CHEN WQ, ZHENG RS, ZHANG SW, et al.Report of cancer incidence and mortality in China, 2013[J].China cancer, 2017, 26 (1) :1-7. (in Chinese) 陈万青, 郑荣寿, 张思维, 等.2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤, 2017, 26 (1) :1-7.

[2]THOMAS MB, CHADHA R, GLOVER K, et al.Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma[J].Cancer, 2007, 110 (5) :1059-1067.

[3]KASEB AO, GARRETTMAYER E, MORRIS JS, et al.Efficacy of bevacizumab plus erlotinib for advanced hepatocellular carcinoma and predictors of outcome:final results of a phase II trial[J].Oncology, 2012, 82 (2) :67-74.

[4]HSU CH, KANG YK, YANG TS, et al.Bevacizumab with erlotinib as first-line therapy in Asian patients with advanced hepatocellular carcinoma:a multicenter phase II study[J].Oncology, 2013, 85 (1) :44-52.

[5]THOMAS MB, MORRIS JS, CHADHA R, et al.Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma[J].J Clin Oncol, 2009, 27 (6) :843-850.

[6]PHILIP A, PHILIP MD, HOLEN KD, et al.Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer[J].Cancer, 2012, 118 (9) :2424-2430.

[7]THOMAS Y, HILDA W, CHAN P, et al.Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease[J].Invest New Drugs, 2012, 30 (6) :2384-2390.

[8]ZHAO RR, DENG YD, YUAN H.Epidemiological and clinical features of primary cancan:ananalys of 236 patients[J].J Clin Hepatol, 2016, 32 (8) :1538-1542. (in Chinese) 赵荣荣, 邓永东, 袁宏.236例原发性肝癌患者流行病学及临床特点分析[J].临床肝胆病杂志, 2016, 32 (8) :1538-1542.

[9]ASNACIOS A, FARTOUX L, ROMANO O, et al.Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma:results of a multicenter phase 2 study[J].Cancer, 2008, 112 (12) :2733-2739.

[10]HANNA K, STEPHEN I, CHARD M, et al.Phase II study of capecitabine, oxaliplatin, and cetuximab for advanced hepatocellular carcinoma[J].Gastrointest Cancer Res, 2011, 4 (3) :78-83.

[11]KANG YK, YAU T, PARK JW, et al.Randomised phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma[J].Ann Oncol, 2015, 26 (12) :2457-2463.

[12]CHAN SL, YEO W, MO F, et al.A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma[J].Cancer, 2017, 123 (20) :3977-3985.

[13]ZHU AX, FINN RS, MULCAHY M, et al.A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer[J].Clin Cancer Res, 2013, 19 (23) :6614-6623.

[14]ZHU AX, PARK J, RYOO BY, et al.Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH) :a randomized, double-blind, multicenter, phase 3 trial[J].Lancet Oncol, 2015, 16 (7) :859-870.

[15]ZHU AX, ANCUKIEWICZ M, SUPKO JG, et al.Efficacy, safety, pharmacokinetics and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma:a phase II study[J].Clin Cancer Res, 2013, 19 (6) :1557-1566.

[16]QIN SK.Apatinib in Chinese patients with advanced hepatocellular carcinoma:a phase II randomized, open-label trial[J].J Clin Oncol, 2014, 32 (15) :17-20.

[17]LU W, JIN XL, YANG C, et al.Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma:a single-center randomized controlled trial[J].Cancer Biol Ther, 2017, 18 (6) :433-438.

[18]LLOVET JM, RICCI S, MAZZAFERRO V, et al.SHARP Investigators Study Group.Sorafenib in advanced hepatocellular carcinoma[J].N Engl J Med, 2008, 359 (4) :378-390.

[19]CHENG AL, KANG YK, CHEN Z, et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phase III randomised, double-blind, placebo controlled trial[J].Lancet Oncol, 2009, 10 (1) :25-34.

[20]JACKSON R, PSARELLI EE, BERHANE S, et al.Impact of viral status on survival in patients receiving sorafenib for advanced hepatocellular cancer:a Meta-analysis of randomized phase III trials[J].J Clin Oncol, 2017, 35 (6) :622-628.

[21]WANG Y, WANG MQ, DUAN F.Prognostic factor analysis of moderate-advanced hepatocellular carcinoma treated with sorafenib[J].J Intervent Radiol, 2017, 26 (3) :258-262. (in Chinese) 王燕, 王茂强, 段峰.索拉非尼治疗中晚期肝癌预后因素分析[J].介人放射学杂志, 2017, 26 (3) :258-262.

[22]TAKAHASHI H, NASU K, MINAMI M, et al.Organ atrophy induced by sorafenib and sunitinib-quantitative computed tomography (CT) evaluation of the pancreas, thyroid gland and spleen[J].Pol J Radiol, 2016, 81:557-565.

[23]XU L, ZHOU DS, ZHAO J, et al.Long-term therapy with sorafenib is associated with pancreatic atrophy[J].J Surg Res, 2015, 199 (2) :314-321.

[24]PATT Y, ROJAS-HERNANDEZ C, EKRAZAD HM, et al.Phase II trial of sorafenib in combination with capecitabine in patients with hepatocellular carcinoma:INST 08-20[J].Oncologist, 2017, 22 (10) :1158-e116.

[25]BRUIX J, TAK WY, GABARRINI A, et al.Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma:multicenter, open-label, phase II safety study[J].Eur J Cancer, 2013, 49 (16) :3412-3419.

[26]BRUIX J, QIN S, MERLE P, et al.Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) :a randomized, double-blind, placebo-controlled, phase 3 trial[J].Lancet, 2017, 389 (10064) :56-66.

[27]IKEDA M, OKUSAKA T, MITSUNAGA S, et al.Safety and pharmacokinetics of lenvatinib in patients with advanced hepatocellular carcinoma[J].Clin Cancer Res, 2016, 22 (6) :1385-1394.

[28]IKEDA K, KUDO M, KAWAZOE S, et al.Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma[J].J Gastroenterol, 2017, 52 (4) :512-519.

[29]ZHUAX, KUDO M, ASSENAT E, et al.Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib:the EVOLVE-1 randomized clinical trial[J].JAMA, 2014, 312 (1) :57-67.

[30]SANOFF HK, KIM R, LVANOVA A, et al.Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma[J].Invest New Drugs, 2015, 33 (2) :505-509.

[31]SANTORO A, RIMASSA L, BORBATH I, et al.Tivantinib for second-line treatment of advanced hepatocellular carcinoma:a randomised, lacebo-controlled phase 2 study[J].Lancet Oncol, 2013, 14 (1) :55-63.

[32]KELLEY RK, VERSLYPE C, COHN AL, et al.Cabozantinib in hepatocellular carcinoma:results of a phase 2 placebo-controlled randomized discontinuation study[J].Ann Oncol, 2017, 28 (3) :528-534.

[33]SANDRINE JF, ARMANDO S, ROBIN KK, et al.A phase 2 study of a novel transforming growth factor-beta (TGF-β1) receptor I kinase inhibitor, LY2157299 monohydrate (LY) , in patients with advanced hepatocellular carcinoma (HCC) [J].J Clin Oncol, 2014, 32 (Suppl 3) :lba173.

[34]CAO Y, AGARWAL R, DITURI F, et al.NGS-based transcriptome profiling reveals biomarkers for companion diagnostics of the TGF-βreceptor blocker galunisertib in HCC[J].Cell Death Dis, 2017, 8 (2) :e2634.

[35]FAN J, ZHOU J, YANG XR.Surgical treatment of hepatocellular carcinoma in the precision medicine era[J].Chin J Dig Surg, 2017, 16 (1) :22-27. (in Chinese) 樊嘉, 周俭, 杨欣荣.精准医学时代的肝癌外科治疗[J].中华消化外科杂志, 2017, 16 (1) :22-27.

施引文献

资源附件(0)

访问统计