Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes.
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.
Siitonen
Timo
T
Department of Internal Medicine, Oulu University Hospital, OYS, Finland. timo.siitonen@ppshp.fi
Timonen
Timo
T
Juvonen
Eeva
E
Terävä
Venla
V
Kutila
Anu
A
Honkanen
Tuomo
T
Mikkola
Maija
M
Hallman
Heikki
H
Kauppila
Marjut
M
Nyländen
Pirkko
P
Poikonen
Eira
E
Rauhala
Auvo
A
Sinisalo
Marjatta
M
Suominen
Merja
M
Savolainen
Eeva-Riitta
ER
Koistinen
Pirjo
P
D000107:Acetylation / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002613:Cheilitis / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D006657:Histones / Q000378:metabolism; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011014:Pneumonia / Q000139:chemically induced; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D006657:Histones; D014635:Valproic Acid; D015474:Isotretinoin; D002117:Calcitriol