title: The role of clofarabine in acute myeloid leukemia.
abstract: Clofarabine is a second-generation purine nucleoside analog that has been synthesized to overcome the limitations and incorporate the best qualities of fludarabine and cladribine. Clofarabine acts by inhibiting ribonucleotide reductase and DNA polymerase, thereby depleting the amount of intracellular deoxynucleoside triphosphates available for DNA replication. Compared to its precursors, clofarabine has an increased resistance to deamination and phosphorolysis, and hence better stability as well as higher affinity to deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside phosphorylation. Since the initiation of the first phase I study of clofarabine in 1993 in patients with hematologic and solid malignancies, clofarabine has demonstrated single-agent antitumor activity in adult acute leukemia, including acute myeloid leukemia (AML). Due to its unique properties of biochemical modulation when used in combination with other chemotherapy drugs, mainly cytarabine, combination regimens containing clofarabine have been evaluated. A review of the English literature was performed that included original articles and related reviews from the MEDLINE (PubMed) database and from abstracts based on the publication of meeting materials. This review describes the development, pharmacology and clinical activity of clofarabine, as well as its emerging role in the treatment of adult patients with AML and myelodysplastic syndrome.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hady
authors.initials: H
authors.lastname: Ghanem
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Maro
authors.initials: M
authors.lastname: Ohanian
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D000077866:Clofarabine; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine