A Review of Liposomal Daunorubicin in the Treatment of Acute Leukemia

Abstract

Liposomal forms of anthracyclines, such as liposomal daunorubicin (L-DNR), have been developed in order to reduce the dose-limiting toxicity, especially cardiotoxicity. Efficacy and reduced toxicity of L-DNR have been demonstrated in severalin vitroand small phase I/II clinical studies. This has led to three recent randomized controlled trials in which efficacy and toxicity of L-DNR in acute myeloid leukemia (AML) patients was evaluated. In elderly, poor-risk AML patients, free DNR was compared with higher doses of L-DNR. This study demonstrated similar complete remission (CR) rates without increasing cardiotoxicity. Overall survival (OS) was slightly better in the L-DNR-arm, but when accounting for risk profiles the OS in the L-DNR arm was significantly better. In pediatric AML, induction therapy with L-DNR was compared with induction with idarubicin. Results showed similar event-free survival (EFS) and OS rates, but less cardiotoxicity with L-DNR. Subgroup analysis demonstrated better results of EFS and OS in core-binding factor AML with L-DNR. Reinduction therapy (fludarabine, cytarabine, granulocyte-colony stimulating factor ± L-DNR) in pediatric relapsed/refractory AML demonstrated higher CR rates in the L-DNR-arm. EFS and OS rates did not significantly improve in the L-DNR arm, but subgroup-analysis showed better results of EFS and OS in core-binding factor AML. The role of L-DNR also seems promising in patients with poor risk, relapsed/refractory ALL, apparently leading to higher CR rates and OS compared with standard regimes. But it should be noted that reports are scarce and no randomized controlled trials have been performed. This article demonstrates that L-DNR improves early treatment response in relapsed AML patients, or equal early treatment response in newly diagnosed AML compared with other anthracyclines, with similar or reduced toxicity. Higher dosages of L-DNR can be administered, without increasing (cardio)toxicity. Nevertheless, prognosis in refractory/ relapsed leukemia remains poor and identifying new therapeutic targets remains necessary—as well as optimization of treatment schedules with conventional agents, including L-DNR.