Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 2012 Dec;70(6):823-32. doi: 10.1007/s00280-012-1976-x. Epub 2012 Sep 26.
The aim of this study was to determine the plasma pharmacokinetics of eribulin mesylate in patients with solid tumors with mild and moderate hepatic impairment.
A phase I, pharmacokinetic study was performed in patients with advanced solid tumors and normal hepatic function or Child-Pugh A (mild) or Child-Pugh B (moderate) hepatic impairment. Treatments were given on day 1 and 8 of a 21-day cycle and consisted of 1.4, 1.1 and 0.7 mg/m(2) eribulin mesylate, for normal hepatic function, Child-Pugh A and B hepatic impairment, respectively. Also safety and anti-tumor activity were determined.
Hepatic impairment increased exposure to eribulin. In patients with Child-Pugh A (N = 7) and Child-Pugh B (N = 5), mean dose-normalized AUC(0-∞) was 1.75-fold (90 % confidence intervals (CI): 1.16-2.65) and 2.48-fold (90 % CI: 1.57-3.92) increased, respectively, compared with patients who have normal function (N = 6). The most frequently reported treatment-related events were alopecia (12/18) and fatigue (7/18) and these were observed across all groups. Nine patients (50 %) had stable disease as best response.
A reduced dose of 1.1 and 0.7 mg/m(2) of eribulin mesylate is recommended for patients with Child-Pugh A or B hepatic impairment, respectively.
本研究旨在确定患有轻度和中度肝损伤的实体瘤患者中甲磺酸艾日布林的血浆药代动力学。
在晚期实体瘤患者中进行了一项 I 期药代动力学研究，这些患者的肝功能正常或 Child-Pugh A（轻度）或 Child-Pugh B（中度）肝损伤。在 21 天周期的第 1 天和第 8 天给予治疗，方案为 1.4、1.1 和 0.7 mg/m²甲磺酸艾日布林，分别用于肝功能正常、Child-Pugh A 和 B 肝损伤的患者。还确定了安全性和抗肿瘤活性。
肝损伤增加了艾日布林的暴露量。在 Child-Pugh A（N = 7）和 Child-Pugh B（N = 5）患者中，与肝功能正常的患者（N = 6）相比，平均剂量标准化 AUC（0-∞）分别增加了 1.75 倍（90 %置信区间（CI）：1.16-2.65）和 2.48 倍（90 % CI：1.57-3.92）。最常报告的与治疗相关的事件是脱发（12/18）和疲劳（7/18），这些事件在所有组中均观察到。9 名患者（50%）的最佳反应为疾病稳定。
建议分别将艾日布林甲磺酸酯的剂量减少至 1.1 和 0.7 mg/m²，用于 Child-Pugh A 或 B 肝损伤的患者。
