Department of Pharmacy, Kobe City Medical Center General Hospital.
Department of Gastroenterology and Hepatology, Kobe City Medical Center General Hospital.
Biol Pharm Bull. 2022;45(3):333-338. doi: 10.1248/bpb.b21-00913.
Proteinuria is one of the most frequently reported adverse events leading to the discontinuation of lenvatinib treatment in patients with advanced hepatocellular carcinoma (HCC). However, there are no reports regarding the risk factors of proteinuria in patients with HCC or patients receiving lenvatinib. We retrospectively reviewed the medical records of patients with HCC receiving lenvatinib at the Kobe City Medical Center General Hospital between April 2018 and December 2020. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors of developing grade ≥2 proteinuria. Among the 37 patients included, 3 patients had grade-1 proteinuria at baseline and 10 patients had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m at baseline. Grades 1, 2, and 3 proteinuria were observed in 15 (40.5%), 10 (27.0%), and 2 (5.4%) patients, respectively, during lenvatinib treatment. The median value of eGFR was significantly lower in patients who developed grade ≥2 proteinuria than those with grade ≤1 proteinuria (59.6 vs. 78.1 mL/min/1.73 m, p = 0.045). Multivariate analysis revealed that pre-existing proteinuria at baseline (hazard ratio (HR), 9.72; 95% confidence interval (CI), 1.29-52.21; p = 0.030), and eGFR <60 mL/min/1.73 m at baseline (HR, 4.49; 95% CI, 1.32-16.07; p = 0.017) were significantly associated with developing grade ≥2 proteinuria. These patients should be monitored carefully, and our preliminary data should be confirmed by further studies.
蛋白尿是导致晚期肝细胞癌（HCC）患者停止仑伐替尼治疗的最常见不良事件之一。然而，目前尚无关于 HCC 患者或接受仑伐替尼治疗患者蛋白尿风险因素的报道。我们回顾性分析了 2018 年 4 月至 2020 年 12 月在神户市医疗中心综合医院接受仑伐替尼治疗的 HCC 患者的病历。蛋白尿严重程度根据不良事件通用术语标准（CTCAE）版本 5.0 分级。采用多变量 Cox 比例风险模型来确定发生≥2 级蛋白尿的风险因素。在纳入的 37 例患者中，3 例患者基线时有 1 级蛋白尿，10 例患者基线时估算肾小球滤过率（eGFR）<60 mL/min/1.73 m。在仑伐替尼治疗期间，分别有 15 例（40.5%）、10 例（27.0%）和 2 例（5.4%）患者出现 1 级、2 级和 3 级蛋白尿。发生≥2 级蛋白尿的患者的 eGFR 中位数明显低于发生≤1 级蛋白尿的患者（59.6 与 78.1 mL/min/1.73 m，p=0.045）。多变量分析显示，基线时存在蛋白尿（风险比（HR），9.72；95%置信区间（CI），1.29-52.21；p=0.030）和基线时 eGFR<60 mL/min/1.73 m（HR，4.49；95% CI，1.32-16.07；p=0.017）与发生≥2 级蛋白尿显著相关。这些患者应密切监测，我们的初步数据应通过进一步研究来确认。
