title: Epigenetic action of decitabine (5-aza-2'-deoxycytidine) is more effective against acute myeloid leukemia than cytotoxic action of cytarabine (ARA-C).
abstract: Treatment of elderly patients with acute myeloid leukemia (AML) with standard cytarabine (ARA-C) chemotherapy can achieve some complete responses (CR), but the median overall survival is less than one year. New approaches should be investigated. The inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (decitabine, DAC), shows effectiveness in these patients, but was not approved by the US Federal Drug Administration. This decision was based on a clinical trial where DAC showed a median survival of 7.0 months as compared to standard ARA-C therapy or supportive care of 5.0 months. However, the difference was not statistically significant. Preclinical data indicate that DAC is much more effective against human AML than ARA-C. The key question is should these preclinical data also be used in the evaluation of new drugs for the clinical treatment of AML? The delayed epigenetic action of DAC is very different than the acute cytotoxic action of ARA-C and should be taken into account in the design clinical trials and evaluation of the response.
authors: Département de pharmacologie, Université de Montréal, Canada. richard.l.momparler@umontreal.ca
authors: Richard L
authors: RL
authors: Momparler
authors: Sylvie
authors: S
authors: Côté
authors: Louise F
authors: LF
authors: Momparler
mesh_terms: D000208:Acute Disease; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003561:Cytarabine / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D000077209:Decitabine; D001374:Azacitidine