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标题: 肝细胞癌:一期和二期临床试验研究药物的最新进展 [打印本页]

作者: StephenW    时间: 2019-10-14 11:17     标题: 肝细胞癌:一期和二期临床试验研究药物的最新进展

Hepatocellular carcinoma: an update on investigational drugs in phase I and II clinical trials
Anne Noonan & Timothy M. Pawlik
Received 02 Aug 2019, Accepted 04 Oct 2019, Accepted author version posted online: 07 Oct 2019, Published online: 12 Oct 2019

    Download citation https://doi.org/10.1080/13543784.2019.1677606 CrossMark Logo CrossMark


ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally. Until recently, systemic therapies for HCC were limited and prognosis for advanced disease generally poor.

Area covered: This article describes some recent phase I and II clinical trials for the treatment of HCC. We performed a search on Pubmed with keywords hepatocellular carcinoma, phase I clinical trial, phase II clinical trial, and immunotherapy. We also searched https://clinicaltrials.gov and identified relevant trials listed as active. Studies in progress or recently reported were conducted using novel therapies based on targets identified through molecular profiling of tumors or based on insights into immune system dysregulation in HCC. We also identified studies using drugs targeting recently discovered biomarkers such as endoglin or aldo-keto reductase 1c3. The major outcomes were safety and efficacy as measured by response rate, progression-free survival or overall survival.

Expert opinion: HCC is a heterogeneous disease resulting from aberrations in intracellular signaling and immune system dysregulation. Thus, a multisystem approach will be required to deliver personalized therapy. Combination therapies are likely to be future options; it is also possible that modulation of the microbiome might form part of future treatment paradigms.
KEYWORDS: Hepatocellular carcinoma, phase I clinical trial, phase II clinical trial, immunotherapy
Additional information
Funding
This paper was not funded.
Article Highlights

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the burden of disease is increasing globally.

    Sorafenib was the only approved therapy from 2007 to 2017.

    Regorafenib was the first new FDA approved agent for the treatment of HCC in the second line setting.

    Since 2017, two tyrosine kinase inhibitors – lenvatinib, and cabozantanib, two PD-1 inhibitors – nivolumab and pembrolizumab, as well as a monoclonal antibody ramucirumab, have all received FDA approval.

    Multiple recent phase I and II clinical trials of investigational drugs for the treatment of HCC are ongoing.

    A multisystem approach will be required to deliver personalized therapy.

    Combination therapies are likely to become future options for patients and it is possible that modulation of the microbiome might form part of future treatment paradigms.

This box summarizes key points contained in the article.

作者: StephenW    时间: 2019-10-14 11:17

肝细胞癌:一期和二期临床试验研究药物的最新进展
安妮·努南(Anne Noonan)和蒂莫西·M·鲍里克(Timothy M.Pawlik)
接收到2019年8月2日,接受了2019年10月4日,接受了作者版本在线发布:2019年10月7日,在线发布:2019年10月12日

    下载引文https://doi.org/10.1080/13543784.2019.1677606 CrossMark徽标CrossMark


抽象

简介:肝细胞癌(HCC)是最常见的原发性肝癌,全球疾病负担正在增加。直到最近,用于HCC的全身治疗仍然受到限制,晚期疾病的预后普遍较差。

涵盖领域:本文介绍了一些用于治疗HCC的近期I和II期临床试验。我们在Pubmed上搜索了关键词肝细胞癌,I期临床试验,II期临床试验和免疫疗法。我们还搜索了https://clinicaltrials.gov,并确定了相关试验被列为有效试验。正在进行的研究或最近报道的研究是基于肿瘤分子轮廓鉴定的靶标或对HCC免疫系统失调的见解,使用新疗法进行的。我们还确定了使用针对最近发现的生物标记物(例如内皮糖蛋白或醛基酮还原酶1c3)的药物进行的研究。主要结果是通过反应率,无进展生存期或总生存期衡量的安全性和有效性。

专家意见:HCC是一种异质性疾病,是由细胞内信号传导异常和免疫系统失调导致的。因此,将需要采用多系统方法来进行个性化治疗。组合疗法可能是未来的选择。微生物组的调节也可能构成未来治疗范例的一部分。
关键词:肝细胞癌,I期临床试验,II期临床试验,免疫治疗
附加信息
资金
该论文未获得资助。
文章重点

    肝细胞癌(HCC)是最常见的原发性肝癌,全球疾病负担正在增加。

    索拉非尼是2007年至2017年唯一获批准的疗法。

    Regorafenib是首个获得FDA批准的新药物,用于二线治疗中的HCC。

    自2017年以来,两种酪氨酸激酶抑制剂lenvatinib和cabo​​zantanib,两种PD-1抑制剂nivolumab和pembrolizumab以及单克隆抗体ramucirumab均已获得FDA批准。

    目前正在进行多项用于治疗HCC的研究药物的I期和II期临床试验。

    提供个性化治疗将需要采用多系统方法。

    组合疗法可能会成为患者未来的选择,微生物组的调节可能会构成未来治疗范例的一部分。

此框总结了文章中包含的关键点。




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