Bioequivalence of two doxorubicin liposome formulations (LY01612 and Caelyx) using free and encapsulated doxorubicin concentrations in Chinese patients with advanced breast cancer

To determine the pharmacokinetic properties and bioequivalence of a reference doxorubicin injectable formulation (Caelyx) and the test formulation, a newly developed doxorubicin hydrochloride liposome injection formulation (LY01612), administered as single bolus doses in Chinese patients with advanced breast cancer. The study was multicentric, randomized, open-label, two-treatment, two-period, two-sequence, single dose with crossover. The dose, equivalent to 50 mg/m2, was administered intravenously on the first day of each 28-day treatment period. Blood samples were collected at appropriate intervals for estimation of Cmax, AUC0-t, and AUC0-∞ for free, encapsulated, and total doxorubicin, as well as partial AUC (AUC0-48h, AUC48h-last) for encapsulated doxorubicin. The 90% confidence intervals (CI) for the geometric mean ratio (GMR) of the primary endpoints for determination of bioequivalence namely, Cmax, AUC0-t, and AUC0-∞ for free doxorubicin and encapsulated doxorubicin, and the 90% CIs for the secondary endpoints Cmax, AUC0-t, and AUC0-∞ for total doxorubicin and partial exposure parameters AUC0-48h and AUC48h-last of encapsulated doxorubicin, were within the range confirming that the two formulations are bioequivalent. The incidence of treatment-emergent adverse events in the test and reference product was 95.7% (44/46) and 100% (42/42), respectively (p > 0.05). The two formulations examined in the cohort of 48 Chinese patients with advanced breast cancer using measurements of free and encapsulated doxorubicin concentrations were bioequivalent. Both agents were well tolerated, and differences were not significant.