Department of Pharmacy, Kanagawa Prefectural Keiyukai Keiyu Hospital; 3-7-3 Minatomirai, Nishi-ku, Yokohama city, Kanagawa.
Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji-city, Tokyo.
Anticancer Drugs. 2024 Jan 1;35(1):89-92. doi: 10.1097/CAD.0000000000001529. Epub 2023 Aug 15.
Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, causes severe hepatotoxicity, a severe adverse event associated with the loss of treatment opportunities. We report a case of liver injury (grade 4) during treatment with abemaciclib, in which the patient was switched to palbociclib and successfully treated with this CDK4/6 inhibitor. A 73-year-old woman with bone metastatic breast cancer (hormone-positive, HER2-negative) was treated with abemaciclib, fulvestrant, denosumab, and precipitated calcium carbonate with cholecalciferol and magnesium carbonate (pCCCM). On day 17, the patient developed skin rashes on her trunk and arms. On day 22, abemaciclib and pCCCM were discontinued due to drug eruption. Grade 3 aspartate aminotransferase (AST) and grade 4 alanine aminotransferase (ALT) levels increased on day 29. Therefore, fulvestrant and denosumab were suspended as the causes of severe hepatotoxicity, in addition to the two drugs suspected of causing the skin eruption. On day 43, AST and ALT levels did not improve, and the patient was referred to a hepatologist. The hepatologist diagnosed hepatotoxicity as a drug-induced liver injury through additional tests and interviews. Fulvestrant treatment was resumed on day 78, and palbociclib on day 92, and denosumab and pCCCM on day 134. On day 287, treatment with the CDK4/6 inhibitor was continued without evidence of liver dysfunction. This case suggests that rechallenge with palbociclib after severe liver injury with abemaciclib may allow for continued treatment with CDK4/6 inhibitors.
阿贝西利是一种细胞周期蛋白依赖性激酶 4/6(CDK4/6)抑制剂,可引起严重的肝毒性,这是一种严重的不良事件,会导致丧失治疗机会。我们报告了一例阿贝西利治疗期间发生的肝损伤(4 级),患者改用帕博西利治疗,并成功接受了这种 CDK4/6 抑制剂的治疗。一名 73 岁女性患有骨转移乳腺癌(激素阳性,HER2 阴性),接受了阿贝西利、氟维司群、地舒单抗和碳酸钙磷复合物(pCCCM)治疗。第 17 天,患者躯干和手臂出现皮疹。第 22 天,由于药物性皮疹,停用了阿贝西利和 pCCCM。第 29 天,丙氨酸氨基转移酶(AST)和天冬氨酸氨基转移酶(ALT)水平升高至 3 级和 4 级。因此,除了怀疑引起皮疹的两种药物外,还暂停了氟维司群和地舒单抗的治疗。第 43 天,AST 和 ALT 水平未改善,患者转至肝病专家处就诊。通过进一步的检查和访谈,肝病专家诊断为药物性肝损伤。第 78 天恢复氟维司群治疗,第 92 天恢复帕博西利治疗,第 134 天恢复地舒单抗和 pCCCM 治疗。第 287 天,继续使用 CDK4/6 抑制剂治疗,无肝功能障碍证据。该病例提示,在阿贝西利引起严重肝损伤后,用帕博西利再挑战可能允许继续使用 CDK4/6 抑制剂治疗。