Elacytarabine – A New Agent in the Treatment of Relapsed/Refractory Acute Myeloid Leukaemia

The prognosis for patients with relapsed acute myeloid leukaemia (AML) is poor, and effective treatments for this patient group remain a substantially unmet clinical need. Elacytarabine is a promising new cytotoxic nucleoside agent made by an esterification reaction between cytarabine and elaidic acid, currently in development for use in the treatment of relapsed/refractory AML. Unlike cytarabine, cellular uptake of elacytarabine is independent of human equilibrative nucleoside transporter-1 (hENT-1) and results in prolonged intracellular retention of the active nucleoside. In addition, elacytarabine inhibits DNA synthesis for twice the duration seen with cytarabine and exhibits a different intracellular distribution. A Phase I trial in patients with AML identified a recommended dose of 2,000 mg/m2/day for five days and showed limited non-haematological side effects, liver toxicity being dose-limiting. Elacytarabine can be safely combined with idarubicin. A recent Phase II trial demonstrated an improved complete remission rate and overall survival with elacytarabine as a single agent in patients with advanced AML, as compared with a historical control group treated with second salvage therapy. Following these encouraging results, the results of an ongoing Phase III clinical trial comparing elacytarabine with the investigator’s choice of standard of care are awaited with interest.