Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients

Abstract

Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) among 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 h. 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 h 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% to 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 drugs were observed.Conclusion: Albumin-bound paclitaxel (QL, HR or ZDTQ; test products) showed bioequivalence to Abraxane® (reference) with lower intra-subject variability, which was less than 16% in all cases, and was well-tolerated in Chinese breast cancer patients. Twenty-two patients are enough for an albumin-bound paclitaxel bioequivalence study.

Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers

“…Breast cancer (BC) is one of the most common malignant tumors in women ( Giri et al, 2018 ; Li et al, 2018 ; Tsoutsou et al, 2018 ). In China, the incidence rate of female breast cancer is increasing each year, and the incidence is second only to cervical cancer ( Yu et al, 2017 ).…”

“…Currently, the drugs used to target HER2 for the treatment of breast cancer primarily include trastuzumab, lapatinib, Pertuzumab and ado-trastuzumab emtansine ( Figueroa-Magalhaes et al, 2014 ; Bartsch and Bergen, 2018 ). Trastuzumab was the first anti-HER2 antibody and has a good therapeutic effect on HER2-positive breast cancer ( Osako et al, 2015 ; Li et al, 2018 ; Zhu et al, 2020 ). Pertuzumab (trade name: Perjeta®) is another HER2 monoclonal antibody that blocks formation of the HER2 dimer and its receptor by binding HER2, inhibiting activation of the PI3K-PKB/Akt signaling pathway, inhibiting the activity of cancer cells, slowing tumor growth, and reducing recurrence rate ( Osako et al, 2015 ; Williams et al, 2017 ; Paek et al, 2019 ).…”

<p>Bioequivalence of paclitaxel protein-bound particles in patients with breast cancer: determining total and unbound paclitaxel in plasma by rapid equilibrium dialysis and liquid chromatography–tandem mass spectrometry</p>

“…Twenty-five patients with breast cancer were enrolled according to the inclusion/exclusion criteria 27. These patients were diagnosed by imaging, cytological or histological examination, or who were considered eligible for the injection of nab-paclitaxel antitumor therapy.…”

Exosomes: Diagnostic Biomarkers and Therapeutic Delivery Vehicles for Cancer

“…Despite providing potent antitumor activity, PTX has finite clinical applications because of its low water solubility, myelosuppression, neurotoxicity, and hypersensitivity. Paclitaxel liposome , and paclitaxel albumin have been developed to encapsulate paclitaxel, which can reduce the therapeutic dose and toxicity of the drug and improve patient tolerance. Exosome-paclitaxel (exoPTX) has been studied to overcome or reverse multidrug resistance (MDR) in cancer cells.…”