The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia.

Détails

ID Serval
serval:BIB_00E198422F61
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia.
Périodique
Cancer
Auteur⸱e⸱s
Kuendgen A., Schmid M., Schlenk R., Knipp S., Hildebrandt B., Steidl C., Germing U., Haas R., Dohner H., Gattermann N.
ISSN
0008-543X (Print)
ISSN-L
0008-543X
Statut éditorial
Publié
Date de publication
01/01/2006
Peer-reviewed
Oui
Volume
106
Numéro
1
Pages
112-119
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article
Publication Status: ppublish
Résumé
Valproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all-trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro.
We used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50-100 mug/mL. Thirty-one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA.
The response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count > 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance.
Future trials should combine VPA with chemotherapy or demethylating agents.
Mots-clé
Acute Disease, Adult, Aged, Aged, 80 and over, Antineoplastic Agents/administration & dosage, Antineoplastic Agents/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Female, Histone Deacetylase Inhibitors, Humans, Leukemia, Myeloid/drug therapy, Leukemia, Myeloid/mortality, Male, Middle Aged, Treatment Outcome, Tretinoin/administration & dosage, Tretinoin/therapeutic use, Valproic Acid/administration & dosage, Valproic Acid/therapeutic use
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/07/2019 13:27
Dernière modification de la notice
21/08/2019 6:36
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