title: Clofarabine in the treatment of myelodysplastic syndromes.
abstract: BACKGROUND
  Clofarabine is a second-generation purine nucleoside analog approved in 2004 for the treatment of pediatric patients with relapsed or refractory acute lymphocytic leukemia (ALL) following failure of at least two prior regimens. Clofarabine is a hybrid of fludarabine and cladribine, designed to overcome the pharmacologic limitations associated with its predecessors, while retaining their beneficial properties. In addition to providing a valuable treatment option for pediatric patients with ALL, clofarabine alone and in combination with cytarabine (Ara-C) has demonstrated substantial activity against myelodysplastic syndrome (MDS), thus rendering this agent a potential therapeutic option for MDS.
  
  
  METHODS
  This review focuses on the pharmacology and clinical activity of clofarabine in MDS, as well as its emerging role in the treatment of MDS. Publications in English were selected from the MEDLINE (PubMed) database, as well articles of interest from bibliographies and abstracts based on the publication of meeting materials.
  
  
  CONCLUSIONS
  DNA-methyltransferase inhibitors are the mainstay of therapy for many patients with MDS who require treatment. Although these agents are very well tolerated and represent a significant advancement in the treatment of MDS by improving transfusion requirements and prolonging survival in various subgroups of patients, response rates are modest and the duration of response is short. In addition to providing a valuable treatment option for pediatric ALL patients, clofarabine has substantial activity against MDS and is well tolerated by elderly patients, thus rendering it a potential therapeutic option.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia , 1515 Holcombe Blvd. Box 428. Houston, TX 77030 , USA +1 713 792 4764 ; +1 713 794 4297 ; ejabbour@mdanderson.org.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bryan
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Hillary
authors.initials: H
authors.lastname: Prescott
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000227:Adenine Nucleotides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077866:Clofarabine; D003561:Cytarabine / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine