Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer

摘要

Purpose: 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. Methods: A randomized, open-label, two-way crossover study was conducted in eligible patients. Patients received with reference or test drugs of 75 mg/m2 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. Results: 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. Conclusion: 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.