title: Pharmacokinetic evaluation of decitabine for the treatment of leukemia.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) is a life-threatening malignancy that primarily afflicts an elderly population. Treatment of elderly patients with intensive chemotherapy is associated with high treatment-related morbidity and mortality. Therefore, less toxic approaches involving low-dose decitabine-based regimens are being explored in this patient population.
  
  
  METHODS
  This drug evaluation article discusses the rationale for targeting aberrant DNA methylation in hematologic malignancies, in particular the myelodysplastic syndromes (MDS) and AML. The authors review the pharmacokinetic data gained from low-dose decitabine, as well as the clinical progress of decitabine in the treatment of hematologic malignancies. Published manuscripts in English were selected from PubMed using a combination of the following search terms: acute myeloid leukemia, pharmacokinetics, decitabine, 5-aza-2'-deoxycytidine, DNA methylation, DNA methyltransferase, myelodysplastic syndrome and leukemia.
  
  
  CONCLUSIONS
  Decitabine has established efficacy in MDS and shown promising activity in AML at low doses. Given decitabine’s favorable toxicity profile and emerging clinical efficacy, decitabine may be a low intensity therapeutic option for elderly patients with AML who are considered unfit for aggressive chemotherapy.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Department of Leukemia, Houston, TX 77030, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bryan
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000367:Age Factors; D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000503:physiopathology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine