Kim Kyung, Jha Reena, Prins Petra A, Wang Hongkun, Chacha Monica, Hartley Marion L, He Aiwu Ruth
Georgetown University Hospital, 3800 Reservoir Road, N.W., Washington, DC, 20007, USA.
Department of Radiology, Georgetown University Hospital, CCC Building, 3800 Reservoir Road, N.W., Washington, DC, 20007, USA.
Cancer Chemother Pharmacol. 2017 Nov;80(5):945-954. doi: 10.1007/s00280-017-3431-5. Epub 2017 Sep 20.
We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation.
Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria). Relevant clinical data were abstracted from patient medical records and reviewed retrospectively.
The median duration of patient treatment was 6.6 weeks, and the median time to disease progression was 12.5 weeks. Most common treatment emergent adverse events were fatigue, diarrhea, and hand-foot skin reaction. Elevated AST and ALT were the most commonly observed laboratory-assessed adverse events, which reached grade 3 status in the Child-Pugh class B patients only. We observed intolerance to regorafenib treatment in one patient who had previously received a liver transplant. We also saw lithium toxicity in one patient receiving long-term lithium treatment, suggesting a potential and unexpected drug-drug interaction with regorafenib.
Taken together, our observations indicate that regorafenib is beneficial in the treatment of patients with advanced HCC who progressed on or demonstrated intolerance to sorafenib therapy; however, careful selection and close monitoring of patients is necessary to maximize the benefit while minimizing the toxicities of regorafenib treatment.
我们报告了2016年6月至2017年1月期间接受瑞戈非尼同情用药治疗的10例晚期肝细胞癌（HCC）患者（分别有7例和3例为Child-Pugh A级和B级）的机构观察结果。这些患者不符合临床试验的严格标准，代表了瑞戈非尼在日常临床情况下的使用情况。
患者接受瑞戈非尼（每日口服160mg）治疗，每4周为一个周期（连续服用3周，停药1周），直至疾病进展（根据mRECIST标准评估）或因毒性而停药（根据CTCAE标准评估）。从患者病历中提取相关临床数据并进行回顾性分析。
患者治疗的中位持续时间为6.6周，疾病进展的中位时间为12.5周。最常见的治疗中出现的不良事件为疲劳、腹泻和手足皮肤反应。AST和ALT升高是最常观察到的实验室评估不良事件，仅在Child-Pugh B级患者中达到3级。我们观察到1例先前接受肝移植的患者对瑞戈非尼治疗不耐受。我们还在1例接受长期锂治疗的患者中发现了锂中毒，提示与瑞戈非尼存在潜在且意外的药物相互作用。
综合来看，我们的观察结果表明，瑞戈非尼对在索拉非尼治疗中进展或不耐受的晚期HCC患者有益；然而，为了使瑞戈非尼治疗的益处最大化同时将毒性最小化，必须仔细选择并密切监测患者。
