Cytarabine has long been an important component of standard chemotherapy for hematological malignancies. Investigations into the mechanism of resistance to this agent have led to new insights into the metabolism of cytarabine. The human equilibrative nucleoside transporter 1 (hENT1), the principal transmembrane transporter of cytarabine, has been identified as an important mediator of drug resistance. Elacytarabine (CP-4055) is a 5′-elaidic acid ester of cytarabine. A lipophilic derivative, this novel agent enters the cell independent of hENT1 and delivers higher intracellular levels of the active cytarabine metabolite in cells resistant to the parent drug. Preclinical studies of elacytarabine show prolonged intracellular retention and significant cytotoxic activity in cytarabine-resistant models. In clinical studies, elacytarabine has been well tolerated, with early response rates of 15-26.7%. In this review, we present the current status of this new agent and discuss its development from chemical synthesis to clinical studies.
ASJC Scopus subject areas
- Pharmacology (medical)