Pharmacokinetics of Daunorubicin Entrapped in Liposomes or Erythrocytes—Phase II Study in Refractory Acute Leukemias

This Phase II study investigates the pharmacokinetics, toxicity, and tolerability of daunorubicin administered in three forms—free (standard), liposome-encapsulated (DaunoXome, DX), and erythrocyte-entrapped (DEE)—in patients with refractory and relapsed acute leukemias. Daunorubicin's efficacy is linked to pharmacokinetic parameters such as peak concentration (PC) and area under the curve (AUC). The free form exhibits rapid distribution and slow elimination, contributing to high cardiotoxicity. DX demonstrates significantly enhanced PC and AUC with prolonged circulation and reduced toxicity. DEE also shows improved AUC and tolerability, but preparation requires strict handling protocols. Results suggest that DX may be effective for relapsed acute promyelocytic leukemia (APL), especially when anthracycline dosage thresholds have been reached. DEE could serve as an alternative to prolonged infusions, particularly in patients with compromised cardiac function. Further randomized studies are needed to confirm long-term efficacy and safety.