索拉非尼在肝癌的治疗：多中心真实世界的研究

StephenW

Sorafenib in the treatment of hepatocellular carcinoma: a multi-centre real-world study

DOI:
    10.3109/00365521.2016.1166518

Adam Doylea**, Philip Marsha, Raghubinder Gillb, Marcia Rodovb, Waled Mohsenb, Poornima Varmac, Thai Hongd, Simone I. Strasserb, Sally Belld, Marno Ryand, Amanda Nicollce, John Lubele, Paul J. Gowf, Michael Anthony Finkg, Stuart Robertsh, William Kemph, Ian Kronborgi, Niranjan Arachchii, Virginia Knighta & Anouk Deva

pages 979-985
Publishing models and article dates explained

    Received: 23 Jan 2016
    Accepted: 12 Mar 2016
    Published online: 10 May 2016


Abstract
Objective: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Material and methods: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Results: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2–3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2–3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Conclusions: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.

   
KEYWORDS

    Adverse effects,
    multivariate analysis,
    progression,
    survival

StephenW

索拉非尼在肝癌的治疗：多中心真实世界的研究

DOI：
    10.3109 / 00365521.2016.1166518

亚当Doylea **，菲利普·玛莎，Raghubinder Gillb，玛西娅Rodovb，Waled Mohsenb，Poornima Varmac，泰国Hongd，西蒙娜一Strasserb，莎莉Belld，Marno Ryand，阿曼达Nicollce，约翰Lubele，保罗J. Gowf，迈克尔·安东尼Finkg，司徒Robertsh，威廉Kemph，伊恩Kronborgi，NIRANJAN Arachchii，弗吉尼亚州Knighta和阿努克·德瓦

979-985页
出版模式和文章解释日期

    收稿日期：2016年1月23日
    接受日期：2016年3月12日
    在线发表时间：2016年5月10日


抽象
目的：索拉非尼是一种口服的多激酶抑制剂，晚期肝细胞癌（HCC）提高生存率。在没有替代疗法，索拉非尼通常持续尽管前进肝脏疾病或肿瘤进展。现实世界中的研究是非常重要的在这些人群中更好地表征结果。我们的目的是审查索拉非尼的使用方式在八个澳大利亚的三级医院，定义与临床结果相关的变量。材料与方法：用索拉非尼肝癌治疗的患者320病历回顾性队列研究。基线临床参数，剂量，不利的影响，和存活从治疗开始收集。时间到影像上的进展和3个月的甲胎蛋白（AFP）水平可用于患者的一个子集。结果：不良反应发生率为79％，要求在31％的患者减少剂量。多变量分析确定死亡率的增加率Child-Pugh分级C（HR 5.52，P = 0.012），ECOG评分2-3（HR 2.84，P = 0.001）和肝外转移（HR 1.54，P = 0.04），用在3个月（HR 0.38，p值= 0.001）的AFP减少至少20％减少死亡率的速率。放射性进展的增加率与ECOG评分2-3（HR 2.34，p值= 0.041）相关联，而放射性进展的减少率与上治疗腹泻的发展（HR 0.55，P = 0.015）相关联。结论：患者的生存Child-Pugh分级丙肝功能或索拉非尼治疗晚期功能障碍性较差，因此日常使用本剂在这些患者中没有出现合理的，特别是考虑到不良反应率很高。在治疗AFP水平可能有助于发现对治疗反应良好。

   
关键词

    不利影响，
    多因素分析，
    进展
    生存