Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes.

Abstract

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.

• Authors: Timo Siitonen, Timo Timonen, Eeva Juvonen, Venla Terävä, Anu Kutila, Tuomo Honkanen, Maija Mikkola, Heikki Hallman, Marjut Kauppila, Pirkko Nyländen, Eira Poikonen, Auvo Rauhala, Marjatta Sinisalo, Merja Suominen, Eeva-Riitta Savolainen, Pirjo Koistinen, Pirjo Koistinen for the Finnish Leukemia Group
• Journal: Haematologica (Haematologica) Vol. 92 Issue 8 Pg. 1119-22 (Aug 2007) ISSN: 1592-8721 [Electronic] Italy
• PMID: 17650442 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Histones
• Valproic Acid
• Isotretinoin
• Calcitriol

Topics

• Acetylation (drug effects)
• Aged
• Aged, 80 and over
• Calcitriol (administration & dosage, adverse effects, therapeutic use)
• Cheilitis (chemically induced)
• Chemical and Drug Induced Liver Injury (etiology)
• Drug Therapy, Combination
• Fatigue (chemically induced)
• Histones (metabolism)
• Humans
• Isotretinoin (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Pneumonia (chemically induced)
• Protein Processing, Post-Translational (drug effects)
• Treatment Outcome
• Valproic Acid (administration & dosage, adverse effects, therapeutic use)