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Epival
Hi Lynn and Margie,
I can only find very difficult articles about Epival (valproic acid). In short it is a drug that affects the growth of malignant cells due to its capability to inhibit histone deacetylation. Aberrant histone deacetylase activity in malignant cells leads to silencing of tumor supressor genes and the malignant cells increases.
"Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia
Kuendgen, Andrea1; Knipp, Sabine; Fox, Frank; Strupp, Corinna; Hildebrandt, Barbara; Steidl, Christian; Germing, Ulrich; Haas, Rainer; Gattermann, Norbert
Annals of Hematology, Volume 84, Supplement 1, December 2005 , pp. 61-66
Abstract:
Valproic acid inhibits histone deacetylase activity and induces differentiation of acute myeloid leukemia (AML) blasts in vitro. We observed clinical responses to valproic acid in patients with myelodysplastic syndrome and AML.
Here, we report follow-up data on 75 patients. Of these, 66 were started on valproic acid monotherapy, with later addition of all-trans retinoic acid in patients who did not respond or relapsed. Nine patients were treated with valproic acid + all-trans retinoic acid from the start. Median treatment duration was 4 months for valproic acid and 2 months for all-trans retinoic acid.
Hematological improvement, according to international working group criteria for MDS, was observed in 18 patients (24%). Median response duration was 4 months. All-trans retinoic acid exerted no additional effect in patients receiving the combination from the start or benefited primary valproic acid nonresponders.
However, of ten valproic acid responders who relapsed, four achieved a second response after addition of all-trans retinoic acid. Response rates were strongly dependent on disease type according to WHO classification.
We found a response rate of 52% in MDS patients with a normal blast count (refractory sideroblastic anemia, refractory cytopenia with multilineage dysplasia, and refractory sideroblastic cytopenia with multilineage dysplasia).
The response rate was 6% in refractory anemia with excess blasts (I + II), 16% in AML, and 0% in chronic myelomonocytic leukemia. Bone marrow blast count was the only variable that predicted responses.
We conclude that valproic acid is clinically useful in low-risk MDS. For patients with high-risk MDS, valproic acid may be combined with chemotherapy or demethylating drugs (for example Vidaza). If patients relapse after an initial response to valproic acid, all-trans retinoic acid has the potential to induce a prolonged second response."
Kind regards
Birgitta-A
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