Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
Cancer Chemother Pharmacol. 2014 Jan;73(1):9-16. doi: 10.1007/s00280-013-2264-0. Epub 2013 Dec 12.
The aim of this study was to compare CKD-810 (test docetaxel) with Taxotere(®) (reference docetaxel) in terms of pharmacokinetics and safety for patients with advanced or metastatic carcinoma.
A randomized, open-label, two-way crossover study was conducted in eligible patients. Patients received with reference or test drugs of 75 mg/m(2) docetaxel by intravenous infusion for 60 min in the first period and the alternative drug in the second period with a washout of 3 weeks. Plasma concentrations of docetaxel were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including the maximum plasma concentration (C(max)) and the area under the concentration-time curve (AUC), were determined by non-compartmental analysis.
A total of 44 patients were included in the study, 21 patients received test drug and 23 received reference drug for the first cycle. The C(max) of docetaxel was 2,658.77 ng/mL for test drug and 2,827.60 ng/mL for reference drug, and two drugs showed no difference with a statistical significance. Time to reach C(max) (T(max)) of CKD-810 (0.94 h) versus reference docetaxel (0.97 h) was also not significantly different. Other pharmacokinetic parameters including the plasma AUC, elimination half-life, and total body clearance exhibited similar values without a significant difference. The most common grade 3 or 4 toxicity was neutropenia (CKD-810 19.5 or 29.3 %; reference docetaxel 14.6 or 41.5 %). Febrile neutropenia was experienced by only one patient in each group. Two patients died of progression of disease during the study.
Docetaxel anhydrous CKD-810 use with patients suffering advanced or metastatic solid malignancies was equivalent to reference docetaxel in terms of pharmacokinetic parameters and safety profile. Additionally, the test and reference drug met the regulatory criteria for pharmacokinetic equivalence.
本研究旨在比较 CKD-810（试验多西他赛）与 Taxotere(®)（参比多西他赛）在晚期或转移性癌患者中的药代动力学和安全性。
在合格的患者中进行了一项随机、开放标签、两周期交叉研究。在第一周期，患者接受 75mg/m(2)多西他赛静脉输注 60 分钟，分别给予参比或试验药物；在第二周期给予另一种药物，洗脱期为 3 周。通过验证的高效液相色谱-串联质谱检测法测定多西他赛的血浆浓度。通过非房室分析确定药代动力学参数，包括最大血浆浓度（C(max)）和浓度-时间曲线下面积（AUC）。
共纳入 44 例患者，21 例患者接受试验药物，23 例患者接受参比药物进行第一周期治疗。试验药物的多西他赛 C(max)为 2,658.77ng/mL，参比药物为 2,827.60ng/mL，两者无统计学差异。CKD-810（0.94 小时）与参比多西他赛（0.97 小时）达到 C(max)的时间（T(max)）也无显著差异。其他药代动力学参数，包括血浆 AUC、消除半衰期和总体清除率，也表现出相似的值，无统计学差异。最常见的 3 级或 4 级毒性为中性粒细胞减少症（CKD-810 为 19.5%或 29.3%；参比多西他赛为 14.6%或 41.5%）。每组仅各有 1 例患者发生发热性中性粒细胞减少症。2 例患者在研究期间死于疾病进展。
在晚期或转移性实体恶性肿瘤患者中使用无水多西他赛 CKD-810 的药代动力学参数和安全性与参比多西他赛相当。此外，试验药物和参比药物符合药代动力学等效性的监管标准。
