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

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 (AUC_0-t), and AUC extrapolated to infinity (AUC_0-∞) 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.