Béchade Dominique, Chakiba Camille, Desjardin Marie, Bécouarn Yves, Fonck Marianne
Institut Bergonié, département d'oncologie médicale, 229, cours de l'Argonne, 33076 Bordeaux cedex, France.
Institut Bergonié, département d'oncologie médicale, 229, cours de l'Argonne, 33076 Bordeaux cedex, France.
Bull Cancer. 2018 Mar;105(3):290-298. doi: 10.1016/j.bulcan.2017.11.015. Epub 2018 Feb 19.
Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which can progress to severe liver injury in a minority of patients if treatment is maintained despite ongoing injury. This risk requires careful patient management to maintain treatment benefit without harm. This review highlights the various mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites and how this leads to toxicity. These critical events depend of the drug-specific characteristics of each TKI and the patient risk factors, especially genetic characterization. With improved understanding of the mechanisms leading to hepatotoxicity, several strategies have been adopted to prevent or treat this side effect. Recommendations on liver function liver test monitoring have been proposed according to each TKI.
酪氨酸激酶抑制剂(TKIs)用于实体癌的靶向治疗。TKIs导致肝脏不良事件的发生率各不相同(5%-25%),如果在持续损伤的情况下仍维持治疗,少数患者的肝脏不良事件可能会进展为严重肝损伤。这种风险需要对患者进行仔细管理,以在不造成伤害的情况下维持治疗益处。本综述重点介绍了特异质性肝毒性的各种机制、反应性代谢产物的形成以及这如何导致毒性。这些关键事件取决于每种TKI的药物特异性特征以及患者风险因素,尤其是基因特征。随着对导致肝毒性机制的深入了解,已采取了多种策略来预防或治疗这种副作用。已根据每种TKI提出了肝功能检查监测的建议。