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白蛋白-胆红素分级提高索拉非尼治疗失败后的肝储备评估:对药物开发的影响。

The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development.

机构信息

Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.

Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.

出版信息

Aliment Pharmacol Ther. 2017 Mar;45(5):714-722. doi: 10.1111/apt.13904. Epub 2017 Jan 24.

DOI:10.1111/apt.13904
PMID:28116800
Abstract

BACKGROUND

Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin-bilirubin (ALBI) grade is a validated index of liver function in patients with HCC.

AIM

To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment.

METHODS

From a prospectively maintained international database of 447 consecutive referrals, we derived 386 eligible patients treated with sorafenib within Barcelona Clinic Liver Cancer C stage (62%), 75% of whom were of Child class A at initiation. Clinical variables at sorafenib discontinuation were analysed for their impact on post-sorafenib overall survival using uni- and multivariable analyses.

RESULTS

Median post-sorafenib overall survival of the 386 eligible patients was 3.4 months and median sorafenib duration was 2.9 months, with commonest causes of cessation being disease progression (68%) and toxicity (24%). At discontinuation, 92 patients (24%) progressed to terminal stage, due to worsening Child class to C in 40 (10%). Median post-sorafenib overall survival in patients eligible for second-line therapies (n = 294) was 17.5, 7.5 and 1.9 months according respectively to ALBI grade 1, 2 and 3 (P < 0.001).

CONCLUSIONS

The ALBI grade at sorafenib discontinuation identifies a subset of patients with prolonged stability of hepatic reserve and superior survival. This may allow improved patient selection for second-line therapies in advanced HCC.

摘要

背景

肝细胞癌(HCC)的药物研发受到疾病异质性的限制,肝储备是影响生存结果的主要因素。ALBI 分级是一种经过验证的 HCC 患者肝功能指标。

目的

检测 ALBI 分级在预测永久性停止索拉非尼治疗的 HCC 患者的索拉非尼后总生存期(PSOS)中的准确性。

方法

从一个前瞻性维护的国际数据库中,我们选择了 386 名符合条件的患者,这些患者接受了索拉非尼治疗,其中巴塞罗那临床肝癌 C 期(62%),75%的患者在开始时为 Child 分级 A。分析索拉非尼停药时的临床变量对索拉非尼后总生存期的影响,采用单变量和多变量分析。

结果

386 名符合条件的患者中位索拉非尼后总生存期为 3.4 个月,中位索拉非尼持续时间为 2.9 个月,最常见的停药原因是疾病进展(68%)和毒性(24%)。在停药时,92 名患者(24%)进展为终末期,其中 40 名(10%)因 Child 分级恶化至 C 级。有资格接受二线治疗的患者(n = 294)的中位索拉非尼后总生存期分别为 ALBI 分级 1、2 和 3 的 17.5、7.5 和 1.9 个月(P < 0.001)。

结论

索拉非尼停药时的 ALBI 分级可识别出一组肝储备稳定且生存时间较长的患者。这可能有助于改善晚期 HCC 二线治疗的患者选择。

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