Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma
Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma
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DOI：
10.1371/journal.pone.0037563
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发表时间：
2012-05-30
期刊：
影响因子：
3.7
通讯作者：
Goldwasser, Francois
中科院分区：
文献类型：
--
作者：
Mir, Olivier;Coriat, Romain;Goldwasser, Francois
背景：索拉非尼在晚期肝细胞癌（HCC）患者中引起频繁的剂量限制性毒性（DLT）。肌肉减少症已与不良的性能状态和缩短生存期的癌症patients.Patients和方法：在我们的机构接受索拉非尼的儿童普氏A型肝炎患者的特点进行了回顾性分析。在每次访视时测定索拉非尼血浆浓度。在治疗的第一个月内记录毒性，并从基线CT扫描确定肌肉减少症。结果：40例患者（30名男性）。11例（27.5%）肌肉减少。18例患者（45%）在治疗的第一个月内发生DLT。肌萎缩症患者发生的DLT显著多于非肌萎缩症患者（82% vs 31%，p = 0.005）。肌肉减少症患者中3级腹泻的发生率显著高于非肌肉减少症患者（45.5% vs 6.9%，p = 0.01），但3级手足综合征反应的发生率并不高（9% vs 17.2%，p = 1）。在第28天，肌肉减少症患者的索拉非尼AUC中位数（n = 17）显著较高（102.4 mg/l. h vs 53.7 mg/l。结论：在患有晚期HCC的肝功能Child Pugh A患者中，肌肉减少症预测索拉非尼暴露和治疗第一个月内DLT的发生。
Background: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients.Patients and Methods: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans.Results: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l. h versus 53.7 mg/l. h, p = 0.013).Conclusions: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.