title: Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity.
abstract: Elderly patients with acute myeloid leukemia (AML) have a poor prognosis. The authors examined the in vitro and clinical activity of the histone deacetylase inhibitor valproic acid (VA) combined with cytosine arabinoside (AraC) in elderly patients with AML unsuited to intensive therapy. For the in vitro studies, primary AML cells from 11 patients were treated with AraC and VA and analyzed for apoptosis, cytostatic effects, differentiation and acetyl histone H3 induction. VA (alone and with AraC) enhanced apoptosis and induced acetyl histone H3. VA inhibited cell proliferation. For the clinical trial, 15 patients were treated with VA and subcutaneous AraC and assessed for toxicity and response. No complete or partial remissions were achieved. In conclusion, VA has in vitro activity against AML and has additional activity with AraC. However, in this study, this combination demonstrated limited clinical activity in elderly patients with AML.
authors.affiliation: Queensland Institute of Medical Research, Herston, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Lane
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Nigel A J
authors.initials: NA
authors.lastname: McMillan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Saunders
authors.forename: Rachel
authors.initials: R
authors.lastname: Murphy
authors.forename: Terrence
authors.initials: T
authors.lastname: Spurr
authors.forename: Colm
authors.initials: C
authors.lastname: Keane
authors.forename: Helen Mar
authors.initials: HM
authors.lastname: Fan
authors.forename: Peter
authors.initials: P
authors.lastname: Mollee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D061251:Primary Cell Culture; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003561:Cytarabine; D014635:Valproic Acid