Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine

Treatment of Acute Myelogenous Leukemia With the Histone Deacetylase Inhibitor Valproic Cid in Combination With All-trans Retinoic Acid (ATRA) and Low Dose Cytarabine

Hypothesis: Combined treatment with valproic acid and ATRA can be used to achieve disease stabilization for a subset of patients with acute myelogenous leukemia (AML), and this effect can be improved without serious toxicity by adding low-dose cytarabine to this treatment. Adult patients >18 years of age who can be included: Elderly patients who cannot achieve standard chemotherapy, patients with relapsed or resistant AML. Treatment: Combined therapy with: Valproic acid, continuous therapy until disease progression ATRA, oral therapy for 14 days every three months Low-dose cytarabine 10 mg/m2 up to 10 injections during week 2 and 3, repeated every 3 months.

Patients to be included: Elderly patients (>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML). Adult patients of any age (>18 years of age) with relapsed or resistant AML who cannot receive conventional therapy. Treatment: Valproic acid to be started on day 1 as continuous therapy until disease progression. ATRA administered from day 8 orally as 22.5 mg/m2 twice daily for 14 days, repeated every third month. Low-dose cytarabine 10 mg/m2 from day 14 and continued as daily injections for up to 10 days, repeated every third month. Supportive therapy is given according to the hospitals general guidelines. Followup: The first 2 days treatment in hospital, later regular out-patient treatment. Controls will include clinical examination, peripheral blood parameters (including serum valproic acid levels), bone marrow samples.

Acute myelogenous leukemia, all-trans retinoic acid, valproic acid, cytarabine, Disease stabilization, survival, toxicity

ATRA: 22.5 mg/m2 twice daily for 2 weeks every third month Valproic acid: continuous therapy, dosage guided by serum levels Cytarabine: 10 mg/m2 once daily for up to 10 days every third month

Inclusion Criteria: Recently diagnosed AML in patients unfit for intensive chemotherapy Patients with relapsed or refractory AML Exclusion Criteria: No informed consent Intolerance to study drugs Serious liver disease

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