Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, the Netherlands.
Eur J Cancer. 2020 May;130:32-38. doi: 10.1016/j.ejca.2020.02.012. Epub 2020 Mar 13.
Abiraterone acetate is approved for the treatment of metastatic prostate cancer. At the currently used fixed dose of 1000 mg once daily in modified fasting state, 40% of patients do not reach the efficacy threshold of a minimum plasma concentration (C) ≥ 8.4 ng/mL and are thereby at risk of decreased treatment efficacy. This study aims to evaluate whether pharmacokinetically (PK) guided abiraterone acetate dosing with a food intervention is feasible and results in an increased percentage of patients with concentrations above the target.
Patients starting regular treatment with abiraterone acetate in modified fasting state were included. Pharmacokinetic analysis was performed 4, 8 and 12 weeks after start of treatment and every 12 weeks thereafter. In case of C < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was recommended. The first step was concomitant intake of abiraterone acetate with a light meal or a snack.
In total, 32 evaluable patients were included, of which 20 patients (63%) had a C < 8.4 ng/mL at a certain time point during treatment. These patients were recommended to take abiraterone acetate concomitantly with food, after which C increased from 6.9 ng/mL to 27 ng/mL (p < 0.001) without additional toxicities. This intervention led to adequate exposure in 28 patients (87.5%).
Therapeutic drug monitoring of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted in a significant increase in C and offers a cost-neutral opportunity to optimise exposure in patients with low C.
醋酸阿比特龙获批用于治疗转移性前列腺癌。在目前使用的禁食状态下 1000mg 固定剂量下，40%的患者未达到最小血浆浓度（C）≥8.4ng/ml 的疗效阈值，因此存在治疗效果降低的风险。本研究旨在评估在进食干预下进行基于药代动力学（PK）的醋酸阿比特龙给药是否可行，以及是否能增加达到目标浓度的患者比例。
纳入开始在禁食状态下接受常规醋酸阿比特龙治疗的患者。在治疗开始后 4、8 和 12 周以及此后每 12 周进行一次药代动力学分析。如果 C<8.4ng/ml 且毒性可接受，则建议进行 PK 指导干预。第一步是同时服用含有少量食物或零食的醋酸阿比特龙。
共纳入 32 例可评估患者，其中 20 例（63%）在治疗过程中的某个时间点 C<8.4ng/ml。这些患者被建议同时进食，此后 C 从 6.9ng/ml 增加到 27ng/ml（p<0.001），且没有额外的毒性。这一干预措施使 28 例（87.5%）患者获得了足够的暴露。
在临床实践中应用了醋酸阿比特龙的治疗药物监测，证明是可行的。同时进食可显著增加 C，为优化 C 低的患者的暴露提供了一种无额外成本的机会。
