Elacytarabine--lipid vector technology overcoming drug resistance in acute myeloid leukemia.

Abstract

INTRODUCTION:

Ara-C (cytarabine arabinoside) is a deoxycytidine analog that has an established role in the treatment of hematologic malignancies, especially acute myeloid leukemia. Resistance to ara-C occurs and impacts negatively on survival. To combat this, an elaidic acid ester of ara-C, called elacytarabine, has been developed. This novel agent is highly efficacious in cells with demonstrable resistance to the parent agent, including in solid tumor xenografts.

AREAS COVERED:

The mechanisms that account for the increased clinical activity of elacytarabine are discussed, including its ability to bypass the specialized transmembrane nucleoside transport system on which ara-C depends, its prolonged retention within the cell and its alternative effect on the cell cycle. The development and synthesis and pharmacokinetics are outlined, with emphasis on lipid vector technology. Ten clinical trials involving elacytarabine, either as monotherapy or part of a combination regimen, have been carried out in both solid tumor and hematologic malignancies. The efficacy and side effect profile results are summarized.

EXPERT OPINION:

Clinical trials in patients with hematological malignancies are reporting very encouraging efficacy results with an acceptable side effect profile. Elacytarabine has the potential to play an important role in the treatment of multiple malignancies in the future and results from an ongoing Phase III clinical trial are eagerly awaited.

• Authors: Aine Carol Burke, Frank James Giles
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 20 Issue 12 Pg. 1707-15 (Dec 2011) ISSN: 1744-7658 [Electronic] England
• PMID: 22040175 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Cytarabine
• 5'-oleoyl cytarabine

Topics

• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics, pharmacology)
• Cytarabine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics, pharmacology)
• Drug Delivery Systems
• Drug Discovery
• Drug Resistance, Neoplasm (drug effects, physiology)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, physiopathology)
• Molecular Targeted Therapy