Cytarabine

Abstract

Cytarabine is an effective chemotherapeutic agent for the treatment various form of leukemias, particularly acute myelogenous leukemia (AML). Action of cytarabine is dependent upon intracellular phosphorylation, via cytidine kinase, to its active metabolite cytosine arabinoside triphosphate (Ara-CTP), the nucleotide responsible for the inhibition of DNA polymerase and can be incorporated in place of normal substrate of DNA synthesis, dCTP. Generally cytarabine is used in combination with an anthracycline in the treatment of AML. These regimens induce high complete response rates in newly diagnosed AML patients. However, clinical outcome is unsatisfactory, as most of the patients will eventually relapse and often with resistant disease and poor response to subsequent therapy. Efforts to improve clinical outcome for refractory or relapsed AML patients have focused on developing more effective combinations of antineoplastic agents. Several studies have shown the achievement of significant progress in the treatment, for instance the combination of topoisomerase-I inhibitor, topotecan or irinotecan, with cytarabine. Moreover high dose cytarabine therapy (HDAC) has represented a major focus of interest in AML clinical research as post-remission treatment. Many studies have demonstrated that repetitive HDAC offers substantial advantage in terms of prolonged disease free survival duration and diminished cumulative incidence of relapse, especially in subtype t(8;21) and inv(16)/t(16;16) AML patients.