Lee Sung-Eun, Choi Kyungmee, Han Seunghoon, Lee Jongtae, Hong Taegon, Park Gab-Jin, Yim Dong-Seok, Min Chang-Ki
aDepartment of Hematology, Seoul St Mary's Hospital bPharmacometrics Institute for Practical Education and Training (PIPET) cDepartment of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, dDivision of Mathematics, College of Science and Technology, Hongik University at Sejong, Korea.
Anticancer Drugs. 2017 Jul;28(6):660-668. doi: 10.1097/CAD.0000000000000506.
The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (Cmax) was significant for the CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038, final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029). Cmax had a tendency to affect the occurrence of BIPN (≥grade 2) (OR=1.064; P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring.
研究了硼替佐米的药代动力学对多发性骨髓瘤（MM）患者的作用，涉及硼替佐米的最大反应以及硼替佐米诱导的周围神经病变（BIPN）的发生情况。评估了35例接受硼替佐米-地塞米松（VD）和硼替佐米-美法仑-泼尼松（VMP）治疗的MM患者在皮下注射硼替佐米治疗的前12周内对硼替佐米的最大反应和BIPN的发生情况。在第1周期的第1天，给药完成后3小时内采集7份全血样本，以获取每位患者给药后3小时内的最大血浆浓度和时间-浓度曲线下面积（AUC0-3）。对35例有完整数据的患者进行分析，总缓解率为91.4%。42.9%的患者观察到完全缓解（CR）。在两种不同模型中，最大血浆浓度（Cmax）对CR率有显著影响[完整模型：比值比（OR）=1.092；P=0.038，最终模型：OR=1.081；P=0.038]。此外，Cmax与无进展生存优势相关。总体而言，48.6%的患者发生了BIPN，包括周围感觉神经病变和神经痛。与VD治疗的患者相比，VMP治疗的患者风险更高（OR=21.662；P=0.029）。Cmax有影响（≥2级）BIPN发生的趋势（OR=1.064；P=0.092）。在使用硼替佐米治疗MM患者的实际临床实践中，药代动力学因素中的Cmax显著影响CR的实现。VMP治疗的患者对BIPN表现出易感性，提示需要更仔细的监测。
