Original Research ARTICLE
Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients
- 1First Hospital, Jilin University, China
Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) in Chinese breast cancer patients.
Methods: Three randomized, open-label, two-period crossover bioequivalence studies were conducted with albumin-bound paclitaxel. Each subject received a single dose of 260 mg/m2 albumin-bound paclitaxel (sponsor 1 [QL, light food], sponsor 2 [HR, fasting], sponsor 3 [ZDTQ, light food]; test) or Abraxane® (reference) and was monitored for 72 hours. Serum concentrations of total paclitaxel and unbound paclitaxel were measured using liquid chromatography/mass spectrometry (LC/MS), and appropriate pharmacokinetic parameters were determined by non-compartmental methods. Safety assessments included adverse events, hematology and biochemistry tests.
Results: The bioequivalence analyses of the QL, HR and ZDTQ products included 24, 23 and 24 patients, respectively. The mean t1/2 was 20.61–27.31 hours for total paclitaxel. Food intake did not affect the pharmacokinetics of paclitaxel. From the comparison of total paclitaxel and unbound paclitaxel, the 90% confidence intervals (CIs) for the ratios of Cmax, AUC0-t, and AUC0-∞ were within 80.00%–125.00%. The intra-subject variability ranged from 6.4%-11% and 9.85%-15.87% for total paclitaxel and unbound paclitaxel, respectively. Almost all subjects in the test and Abraxane® (reference) groups experienced mild or moderate adverse events. No fatal AEs or study drug injection site reactions related to these drug were observed.
Conclusion: Albumin-bound paclitaxel (QL, HR or ZDTQ; test products) showed bioequivalence to Abraxane® (reference) with lower intra-subject variability and less than 16% in all cases, and were well-tolerated in Chinese breast cancer patients. 22 patients is enough for Albumin-bound paclitaxel bioequivalence study.
Keywords: Cancer, albumin-bound, Paclitaxel, Bioequivalence, variability
Received: 12 Aug 2018;
Accepted: 08 Nov 2018.
Edited by:Carmen Alvarez-Lorenzo, Universidade de Santiago de Compostela, Spain
Reviewed by:Marcello Locatelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
Ayesha N. Shajahan-Haq, Georgetown University, United States
Copyright: © 2018 Ding, ZHU, LIU, WU, LI, GAO and ZHANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. HONG ZHANG, First Hospital, Jilin University, Changchun, Jilin Province, China, email@example.com