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晚期肝细胞癌的全身治疗:寻找新药物以加入索拉非尼,丰富有效的治疗手段。

Systemic treatment for advanced hepatocellular carcinoma: the search of new agents to join sorafenib in the effective therapeutic armamentarium.

作者信息

Ribeiro de Souza Andrea, Reig Maria, Bruix Jordi

机构信息

a Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Center of Biomedical Research in Hepatic and Digestive Diseases of the Ministry of Science and Innovation (CIBERehd) , Hospital Clínic- IDIBAPS; University of Barcelona , Barcelona , Spain.

出版信息

Expert Opin Pharmacother. 2016 Oct;17(14):1923-36. doi: 10.1080/14656566.2016.1225722.

Abstract

INTRODUCTION

Hepatocelullar carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite the implementation of screening programs for high-risk individuals, a significant proportion of patients present with advanced disease at the moment of diagnosis.

AREAS COVERED

In this review we will focus in the current treatment of advanced HCC, the research that has been done in the past few years, the achievements and failures in this setting and future perspectives.

EXPERT OPINION

Sorafenib was the first drug that has shown to increase survival in patients with advanced hepatocelullar carcinoma with an adequate safety profile. Recently, regorafenib was reported to improve survival in a second line randomised placebo controlled phase 3 clinical trial, which represents a major breakthrough in this field after many disappointing results coming from several clinical trials. However, still there is an unmet need for an effective and tolerable treatment for patients who progressed and/or have intolerance to sorafenib. The ultimate goal of the research is to provide drugs that improve survival with acceptable adverse events. Understanding of mechanisms of hepatocarcinogesis, individualizing therapy according to the profile of the population and finding reliable surrogate end-points for survival for early phase trials with new agents should improve the likelihood of achieving these objectives.

摘要

引言

肝细胞癌(HCC)是全球癌症相关死亡的第三大主要原因。尽管对高危个体实施了筛查计划,但仍有相当一部分患者在诊断时已处于疾病晚期。

涵盖领域

在本综述中,我们将聚焦于晚期HCC的当前治疗、过去几年所开展的研究、此背景下的成就与失败以及未来展望。

专家观点

索拉非尼是首个被证明可提高晚期肝细胞癌患者生存率且安全性良好的药物。最近,瑞戈非尼在一项二线随机安慰剂对照3期临床试验中被报道可改善生存率,在多项临床试验取得令人失望的结果之后,这代表了该领域的一项重大突破。然而,对于那些疾病进展和/或对索拉非尼不耐受的患者,仍然迫切需要一种有效且可耐受的治疗方法。该研究的最终目标是提供能在可接受的不良事件情况下提高生存率的药物。了解肝癌发生机制、根据人群特征进行个体化治疗以及为新药早期试验找到可靠的生存替代终点,应会提高实现这些目标的可能性。

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