Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia

Abstract

VYXEOS™ is a liposomal-encapsulated formulation of daunorubicin and cytarabine delivering a fixed, synergistic 1:5 molar ratio (hereafter referred to as daunorubicin/cytarabine liposome). Daunorubicin/cytarabine liposome is approved in several countries worldwide for the treatment of adults with therapy-related acute myeloid leukaemia (tAML) and AML with myelodysplasia-related changes (MRC). Approval was based on its clinical benefit in older patients with newly diagnosed high-risk/secondary AML in a pivotal phase III trial. In this study, daunorubicin/cytarabine liposome significantly prolonged overall survival (OS) and event-free survival (EFS) relative to conventional chemotherapy with cytarabine plus daunorubicin (hereafter referred to as 7 + 3). Daunorubicin/cytarabine liposome was also associated with significantly higher rates of complete remission (CR) and CR with incomplete haematological recovery (CRi) compared with 7 + 3. Daunorubicin/cytarabine liposome had an acceptable tolerability profile in older patients with newly diagnosed high-risk/secondary AML. The safety profile of daunorubicin/cytarabine liposome, including types and severities of adverse events, was generally similar to that of 7 + 3. Therefore, daunorubicin/cytarabine liposome is an important treatment option for adults with newly diagnosed tAML or AML-MRC.

Recent Progress in Bioconjugation Strategies for Liposome-Mediated Drug Delivery

“…Daunorubicin can be encapsulated post-liposome formation by dissolving in ethylenediaminetetraacetic acid (EDTA) buffer at neutral pH, then incubating with cytarabine-loaded liposomes [123]. Patients in clinical trials receiving Vyxeos ® had an overall median survival of 9.63 months versus 5.59 months on conventional treatment, due to increased efficacy from the synergistic effect of the coencapsulated drugs [119,124]. However, despite these benefits, notable toxicity was found in some patients during phase III trials (>20% incidence) including febrile neutropenia, bacteremia, and pneumonia, and treatment had to be discontinued in 18% of recipients due to side effects; despite this, the overall safety profile was similar to conventional chemotherapy [124].…”

Serine, glycine and one‑carbon metabolism in cancer (Review)

“…One of the major challenges for cancer biology is to find novel and effective therapeutic targets that can be used for interventions with chemically selective pharmaceuticals in different patients. Antimetabolite drugs (antifolates) are a landmark in cancer chemotherapy and are still the most widely used drugs in medical oncology (Table I) (125)(126)(127)(128)(129)(130)(131)(132)(133)(134). Among the antifolates, methotrexate and pemetrexed are effective inhibitors of DHFR, which can reduce the THF pool and prevent cell proliferation (135,136).…”

Biomimetic, Hypoxia‐Responsive Nanoparticles Overcome Residual Chemoresistant Leukemic Cells with Co‐Targeting of Therapy‐Induced Bone Marrow Niches

“…However, most of these successes have been for solid tumor indications, while nanomedicines have had more limited impact on hematological malignancies such as leukemia 1a,2. Notably, the recently approved Vyxeos (liposome‐encapsulated daunorubicin‐cytarabine) prolonged 3.7 month overall survival in acute myeloid leukemia (AML) patients, highlighting the potential for nanomedicine and in particular co‐delivered drugs for leukemia management …”