Kamimura Kenya, Shinagawa-Kobayashi Yoko, Goto Ryo, Ogawa Kohei, Yokoo Takeshi, Sakamaki Akira, Abe Satoshi, Kamimura Hiroteru, Suda Takeshi, Baba Hiroshi, Tanaka Takayuki, Nozawa Yoshizu, Koyama Naoto, Takamura Masaaki, Kawai Hirokazu, Yamagiwa Satoshi, Aoyagi Yutaka, Terai Shuji
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, Minami-Uonuma, Niigata, Japan.
Cancer Manag Res. 2018 Apr 17;10:805-813. doi: 10.2147/CMAR.S159370. eCollection 2018.
Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms.
To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow.
A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow ( = 0.009) and significantly decreased occurrence of HFS ( = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period ( = 0.035).
The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.
索拉非尼(SOR)是一种可延长肝细胞癌(HCC)患者生存期的分子药物。因此,对于较长时间的持续用药而言,副作用的管理至关重要。在各种副作用中,手足综合征(HFS)最为常见,30%-50%的患者会出现,且常导致索拉非尼停药。然而,其机制尚未阐明,也未报道针对该症状的有效预防方法。因此,本研究旨在分析其机制并制定针对该症状的有效预防方案。
为评估索拉非尼诱导HFS的机制,在用索拉非尼治疗的病例中,通过多普勒超声、热成像和激光散斑血流图仔细监测手足的外周血流,并评估其作用。然后,通过监测症状的发生情况和外周血流,研究据报道可改善外周血流的鲣鱼汤(DBB)对预防该症状的效果。
本研究共纳入25例患者。总共有8例患者出现HFS,所有病例的外周血流均显著减少。与对照组相比,DBB使血流增加(P = 0.009),并显著降低了HFS的发生率(P = 0.005)。多变量分析表明,摄入DBB是无HFS生存期的显著独立影响因素(P = 0.035)。
索拉非尼诱导HFS的机制涉及外周血流减少,摄入DBB可通过维持血流有效预防该综合征的发生。