A multicenter, randomized, open label, two formulation, crossover bioequivalence trial of doxorubicin hydrochloride liposomal injection in Chinese patients with metastatic breast cancer

J Cancer Res Clin Oncol. 2025 Jan 22;151(1):41. doi: 10.1007/s00432-025-06086-0.

Abstract

Purpose: The primary objectives of this trial were aimed at exploring the pharmacokinetic profiles and the human bioequivalence of an intravenous liposomal injection of doxorubicin hydrochloride in comparison with a reference formulation in Chinese patients diagnosed with metastatic breast cancer.

Methods: To achieve these goals, the trial employed a randomized, open-label, two-formulation crossover dosing strategy among Chinese patients with metastatic breast cancer. Pharmacokinetic (PK) evaluation was conducted through the collection of blood samples, and the liquid chromatography tandem mass spectrometry (LC/MS/MS) method was leveraged to quantify plasma concentrations of both liposome-encapsulated doxorubicin and non-encapsulated doxorubicin in patients. Throughout the trial, all adverse events observed in the patients were meticulously assessed.

Results: The results indicated that the maximum concentration (Cmax), AUC from time zero to the last measurable concentration (AUC0-t), and AUC extrapolated to infinity (AUC0-∞) of in vivo non-encapsulated doxorubicin after administration of both formulations fell within the 80.00%-125.00% range at a 90% confidence interval.

Conclusion: These findings strongly indicated that the tested formulations were bioequivalent to the reference formulation. The results also demonstrated that both formulations were well-tolerated, further establishing their safety profile in the context of metastatic breast cancer treatment.

Trial registration: Chinadrugtrials.org.cn Identifier: CTR20200878.

Keywords: Bioequivalence test; Breast cancer; Doxorubicin hydrochloride liposomes; Pharmacokinetics; Safety.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic* / administration & dosage
  • Antibiotics, Antineoplastic* / pharmacokinetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • China
  • Cross-Over Studies*
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / analogs & derivatives
  • Doxorubicin* / pharmacokinetics
  • East Asian People
  • Female
  • Humans
  • Liposomes
  • Middle Aged
  • Neoplasm Metastasis
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics
  • Therapeutic Equivalency*

Substances

  • Doxorubicin
  • liposomal doxorubicin
  • Antibiotics, Antineoplastic
  • Polyethylene Glycols
  • Liposomes