Chan Stephen L, Yeo Winnie
Stephen L Chan, Winnie Yeo, Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
World J Gastroenterol. 2014 Mar 28;20(12):3135-45. doi: 10.3748/wjg.v20.i12.3135.
A growing number of multi-targeted tyrosine kinase inhibitor (TKI) has undergone testing for hepatocellular carcinoma (HCC). Unfortunately, this enthusiasm has recently been discouraged by a number of negative phase III studies on several anti-angiogenic TKIs in HCC. Several postulations have been made to account for this phenomenon, namely the plateau effects of anti-angiogenesis approach, the heterogeneity of HCC in terms of background hepatitis/cirrhosis and tumor biology, as well as the way how clinical trials are designed. Regardless of the underlying reasons, these results suggested that alternative strategies are necessary to further develop systemic therapy for HCC. Several new strategies are currently evaluated: for examples, molecular agents with activities against targets other than vascular endothelial growth factor receptor are being evaluated in on-going clinical trials. In addition, different approaches of targeted agents in combination with various treatment modalities, such as concurrently with another molecular agent, cytotoxic chemotherapy or transarterial chemoembolization, are being developed. This review aims to give a summary on the results of recently released clinical trials on TKIs, followed by discussion on some of the potential novel agents and combinational approaches. Future directions for testing innovative systemic agents for HCC will also be discussed.
越来越多的多靶点酪氨酸激酶抑制剂（TKI）已针对肝细胞癌（HCC）进行了测试。遗憾的是，最近一些关于HCC中几种抗血管生成TKI的III期阴性研究给这种热情泼了冷水。针对这一现象有多种推测，即抗血管生成方法的平台效应、HCC在背景性肝炎/肝硬化及肿瘤生物学方面的异质性，以及临床试验的设计方式。无论潜在原因是什么，这些结果表明，有必要采用替代策略来进一步开发HCC的全身治疗方法。目前正在评估几种新策略：例如，正在进行的临床试验中正在评估针对血管内皮生长因子受体以外靶点具有活性的分子药物。此外，正在开发靶向药物与各种治疗方式联合的不同方法，如与另一种分子药物、细胞毒性化疗或经动脉化疗栓塞同时联合。本综述旨在总结近期发布的关于TKI的临床试验结果，随后讨论一些潜在的新型药物和联合方法。还将讨论测试HCC创新全身药物的未来方向。
