Elacytarabine, a novel 5'-elaidic acid derivative of cytarabine, and idarubicin combination is active in refractory acute myeloid leukemia.
Cytarabine (ara-C, [1-d-arabinofuranosylcytosine]), enters ells primarily as a false substrate through specialized nucleoside ransporter proteins, predominantly hENT1 (the human equilirative nucleoside transporter). Reduced hENT1 expression and ctivity is associated with adverse therapeutic outcomes and educed cytotoxicity for patients treated with cytarabine [1,2]. atients with AML and low hENT1 expression have reduced isease-free survival [1,3]. Elacytarabine (CP-4055) (Fig. 1), the ipophilic 5′-elaidic acid ester of cytarabine, enters cells indepenently of hENT1. Preclinical studies of elacytarabine demonstrate ctivity in cytarabine-resistant cell lines and in animal models with umor xenografts [4,5]. Elacytarabine may thus be active in patients ith leukemia for whom cytarabine is ineffective [6–8]. We conucted a study to determine DLT, establish the pharmacokinetics PK) and toxicity profiles and to obtain a preliminary assessment f activity of elacytarabine CIV combined with idarubicin in adult atients with refractory AML.