肝细胞癌的全身治疗：挑战与未来展望
Systemic treatments for hepatocellular carcinoma: challenges and future perspectives.
作者信息
Tovoli Francesco, Negrini Giulia, Benevento Francesca, Faggiano Chiara, Goio Elisabetta, Granito Alessandro
机构信息
Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy.
出版信息
Hepat Oncol. 2018 Feb 8;5(1):HEP01. doi: 10.2217/hep-2017-0020. eCollection 2018 Jan.
Abstract
Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.
摘要
近十年来，索拉非尼一直是唯一获批用于肝细胞癌（HCC）的全身治疗药物。最近，两种新药在两项III期研究中显示出阳性结果。RESORCE试验确定瑞戈非尼是对索拉非尼治疗进展的患者有效的二线治疗药物，REFLECT试验表明乐伐替尼作为一线治疗药物不劣于索拉非尼。在这些试验之后，治疗方案将以抗VEGFR药物为主导，三种不同的分子显示出已证实的抗癌活性。一些尚未解决的问题仍然存在，在取得了有前景的初步结果之后，不同的免疫治疗试验正在进行中。在这篇综述中，我们分析了：索拉非尼治疗患者的最新进展；RESORCE和REFLECT试验的结果；以及正在进行的III期临床试验。最后，我们讨论了它们如何解决当前的问题，并可能重塑HCC全身治疗的未来。
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本文引用的文献
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Hepat Oncol. 2016 Apr;3(2):119-136. doi: 10.2217/hep-2015-0006. Epub 2016 Mar 23.
2
The clinical role of 'liquid biopsy' in hepatocellular carcinoma.“液体活检”在肝细胞癌中的临床作用。
Hepat Oncol. 2016 Jan;3(1):45-55. doi: 10.2217/hep.15.38. Epub 2015 Nov 30.
3
The biological and clinical challenge of liver cancer heterogeneity.肝癌异质性的生物学和临床挑战。
Hepat Oncol. 2014 Oct;1(4):349-353. doi: 10.2217/hep.14.18. Epub 2014 Dec 11.
4
Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.ADI-PEG 20 二线治疗联合最佳支持治疗对比安慰剂联合最佳支持治疗晚期肝细胞癌的 III 期随机研究。
Ann Oncol. 2018 Jun 1;29(6):1402-1408. doi: 10.1093/annonc/mdy101.
5
Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions.肝细胞癌且对索拉非尼耐药或不耐受患者的最佳治疗：挑战与解决方案
J Hepatocell Carcinoma. 2017 Nov 8;4:131-138. doi: 10.2147/JHC.S124366. eCollection 2017.
6
Current immunotherapeutic strategies in hepatocellular carcinoma: recent advances and future directions.肝细胞癌的当前免疫治疗策略：最新进展与未来方向
Therap Adv Gastroenterol. 2017 Oct;10(10):805-814. doi: 10.1177/1756283X17722061. Epub 2017 Aug 11.
7
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Eur J Cancer. 2017 Nov;86:135-142. doi: 10.1016/j.ejca.2017.08.036. Epub 2017 Oct 4.
8
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9
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Target Oncol. 2017 Dec;12(6):795-803. doi: 10.1007/s11523-017-0522-5.
10
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Dig Liver Dis. 2017 Sep;49(9):1043-1049. doi: 10.1016/j.dld.2017.06.008. Epub 2017 Jun 23.
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