Ivanyi Philipp, Eggers Hendrik, Hornig Mareike, Kasper Bernd, Heissner Klaus, Kopp Hans-Georg, Kirstein Martha, Ganser Arnold, Grünwald Viktor
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany.
Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, University of Heidelberg, D-68167 Mannheim, Germany.
Mol Clin Oncol. 2020 Dec;13(6):72. doi: 10.3892/mco.2020.2143. Epub 2020 Sep 21.
Regorafenib is a multi-target tyrosine kinase inhibitor that has been approved for the treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors (GIST). Severe hepatobiliary toxicity has been reported in patients with colorectal cancer treated with regorafenib, but not in those with GIST. Therefore, the aim of the present study was to investigate the incidence and clinical course of regorafenib-associated hepatic toxicity (HT) in patients with GIST in a real-world setting. Patients with metastatic GIST treated with regorafenib between September 2012 and May 2014 at three German tertiary care centers were followed up until August 2017. Patient records were retrospectively analyzed and descriptive statistics were employed. HT was defined as alterations in the serum values of aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase and bilirubin (according to the Common Terminology Criteria for Adverse Events, version 4.0), and/or corresponding clinical signs. The time to clinical progression and the overall survival were calculated by Kaplan-Meier curves. Overall, 21 patients were treated with regorafenib and 5 (23.5%) of those heavily pretreated patients suffered from severe HT during regorafenib treatment. In 4 (80%) of these cases, regorafenib treatment was continued, optimizing individual treatment benefit. Clinical monitoring and adequate therapy management are crucial for ensuring continuation of regorafenib treatment in order to achieve an optimal clinical outcome.
瑞戈非尼是一种多靶点酪氨酸激酶抑制剂，已被批准用于治疗转移性结直肠癌、晚期肝细胞癌和转移性胃肠道间质瘤（GIST）。有报道称，接受瑞戈非尼治疗的结直肠癌患者会出现严重的肝胆毒性，但GIST患者未出现这种情况。因此，本研究的目的是在实际临床环境中调查GIST患者中与瑞戈非尼相关的肝毒性（HT）的发生率和临床病程。对2012年9月至2014年5月期间在德国三家三级医疗中心接受瑞戈非尼治疗的转移性GIST患者进行随访，直至2017年8月。对患者记录进行回顾性分析并采用描述性统计方法。HT定义为天冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转移酶、碱性磷酸酶和胆红素的血清值改变（根据不良事件通用术语标准4.0版），和/或相应的临床体征。通过Kaplan-Meier曲线计算临床进展时间和总生存期。总体而言，21例患者接受了瑞戈非尼治疗，其中5例（23.5%）接受过大量预处理的患者在瑞戈非尼治疗期间出现了严重HT。在其中4例（80%）病例中，继续进行瑞戈非尼治疗，以优化个体治疗效益。临床监测和适当的治疗管理对于确保继续使用瑞戈非尼治疗以实现最佳临床结果至关重要。
