Phase II Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Author:

Abou-Alfa Ghassan K.1,Schwartz Lawrence1,Ricci Sergio1,Amadori Dino1,Santoro Armando1,Figer Arie1,De Greve Jacques1,Douillard Jean-Yves1,Lathia Chetan1,Schwartz Brian1,Taylor Ian1,Moscovici Marius1,Saltz Leonard B.1

Affiliation:

1. From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre René Gauducheau, Nantes, France

Abstract

Purpose This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients. Methods Patients with inoperable HCC, no prior systemic treatment, and Child–Pugh (CP) A or B, received continuous, oral sorafenib 400 mg bid in 4-week cycles. Tumor response was assessed every two cycles using modified WHO criteria. Sorafenib pharmacokinetics were measured in plasma samples. Biomarker analysis included phosphorylated extracellular signal regulated kinase (pERK) in pretreatment biopsies (immunohistochemistry) and blood-cell RNA expression patterns in selected patients. Results Of 137 patients treated (male, 71%; median age, 69 years), 72% had CP A, and 28% had CP B. On the basis of independent assessment, three (2.2%) patients achieved a partial response, eight (5.8%) had a minor response, and 46 (33.6%) had stable disease for at least 16 weeks. Investigator-assessed median time to progression (TTP) was 4.2 months, and median overall survival was 9.2 months. Grade 3/4 drug-related toxicities included fatigue (9.5%), diarrhea (8.0%), and hand–foot skin reaction (5.1%). There were no significant pharmacokinetic differences between CP A and B patients. Pretreatment tumor pERK levels correlated with TTP. A panel of 18 expressed genes was identified that distinguished “nonprogressors” from “progressors” with an estimated 100% accuracy. Conclusion Although single-agent sorafenib has modest efficacy in HCC, the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3