Department of Endocrine Neoplasia & Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Semin Oncol. 2019 Feb;46(1):57-64. doi: 10.1053/j.seminoncol.2018.11.004. Epub 2018 Dec 21.
Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, RET, KIT, and platelet-derived growth factor receptor-α. Lenvatinib is approved as a monotherapy for the treatment of radioiodine-refractory differentiated thyroid cancer and in combination with everolimus for the second-line treatment of advanced renal cell carcinoma. Lenvatinib is also under investigation for the treatment of several malignancies including unresectable hepatocellular carcinoma. Although lenvatinib is associated with favorable efficacy, it is associated with adverse events (AEs) that the clinician will have to closely monitor for and proactively manage. Most of these AEs are known class effects of VEGF-targeted therapies, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. This review summarizes the safety profile of lenvatinib and offers guidance for the management of both frequent and rare AEs. We discuss the potential mechanisms underlying these AEs and present practical recommendations for managing toxicities. The development of treatment plans that include prophylactic and therapeutic strategies for the management of lenvatinib-associated AEs has the potential to improve patient quality of life, optimize adherence, minimize the need for dose reductions, treatment interruptions, or discontinuations, and maximize patient outcomes.
仑伐替尼是一种多激酶抑制剂，可抑制血管内皮生长因子 (VEGF) 受体 1-3、成纤维细胞生长因子受体 1-4、RET、KIT 和血小板衍生生长因子受体-α。仑伐替尼被批准用于治疗放射性碘难治性分化型甲状腺癌的单药治疗，以及联合依维莫司用于晚期肾细胞癌的二线治疗。仑伐替尼也在研究用于治疗多种恶性肿瘤，包括不可切除的肝细胞癌。尽管仑伐替尼具有良好的疗效，但它也与不良事件 (AE) 相关，临床医生需要密切监测并主动管理。这些 AE 大多是 VEGF 靶向治疗的已知类别效应，包括高血压、腹泻、疲劳或乏力、食欲下降和体重减轻。本综述总结了仑伐替尼的安全性概况，并为管理常见和罕见 AE 提供了指导。我们讨论了这些 AE 的潜在机制，并提出了管理毒性的实用建议。制定包括预防和治疗策略的治疗计划，以管理仑伐替尼相关 AE，有可能改善患者的生活质量，优化依从性，最大限度地减少减少剂量、治疗中断或停药的需要，并最大限度地提高患者的治疗效果。
