Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan
Anticancer Res. 2020 Jul;40(7):4173-4182. doi: 10.21873/anticanres.14417.
BACKGROUND/AIM: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of cancers. Sorafenib, an oral multi-target TKI, improves the median overall survival time in patients with hepatocellular carcinoma (HCC). It also inhibits the absorption of carnitine by down-regulating the human organic cationic transporter OCTN2 located largely in the small intestinal mucosa and skeletal muscle. The aim of the study was to determine, by assessing carnitine metabolism, whether sarcopenia is induced in patients with HCC who are receiving sorafenib.
This retrospective study included 110 adult Japanese patients with liver cirrhosis and HCC who received sorafenib. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment, and serum carnitine fraction and myostatin levels were measured. Cross-sectional areas (cm) of the skeletal muscles at the third lumbar vertebra level were determined by manually outlining computed tomography images before and after treatment. The cross-sectional areas were normalized for height [skeletal muscle index (SMI), cm/m].
Patients were allocated to two groups according to Child-Pugh (CP) class; 81 had CP-A liver function, and 29 had CP-B. SMI after treatment was significantly lower than that before treatment in both groups. Serum levels of total carnitine and free carnitine after treatment were significantly lower than those before treatment in both groups. There were no differences in serum levels of myostatin before and after treatment in either group.
Sorafenib might decrease serum levels of carnitine by inhibiting carnitine absorption. Decreasing of serum levels of carnitine might lead to presarcopenia.
背景/目的：酪氨酸激酶抑制剂（TKIs）改变了癌症的治疗方式。索拉非尼是一种口服多靶点 TKI，可延长肝细胞癌（HCC）患者的中位总生存期。它还通过下调主要位于小肠黏膜和骨骼肌的人有机阳离子转运体 OCTN2 来抑制肉碱的吸收。本研究旨在通过评估肉碱代谢来确定接受索拉非尼治疗的 HCC 患者是否会发生肌肉减少症。
这是一项回顾性研究，纳入了 110 例接受索拉非尼治疗的成年日本肝硬化合并 HCC 患者。索拉非尼的剂量为 200-800mg/天，治疗 4 周。在治疗前后采集血样，检测血清肉碱分数和肌肉生长抑制素水平。在治疗前后手动勾画 CT 图像，测量第 3 腰椎水平骨骼肌的横截面积（cm）。将横截面积按身高进行归一化[骨骼肌指数（SMI），cm/m]。
根据 Child-Pugh（CP）分级将患者分为两组；81 例 CP-A 肝功能，29 例 CP-B。两组治疗后 SMI 均明显低于治疗前。两组治疗后总肉碱和游离肉碱血清水平均明显低于治疗前。两组治疗前后肌肉生长抑制素血清水平无差异。
索拉非尼可能通过抑制肉碱吸收来降低肉碱血清水平。肉碱血清水平的降低可能导致预肌肉减少症。
