A Study to Investigate Treatment of HU and VPA, or 6-MP and VPA in Unfit AML/HR-MDS Patients

Hydroxyurea (HU/hydroxycarbamide) is a hydroxylated analogue of urea which prevents DNA synthesis by inhibiting the activity of ribonucleotide reductase (RNR). HU has been used to treat a variety of diseases. As an antineoplastic drug, HU has some advantages. It may be used by ambulatory patients and has relatively few side effects, which are relieved almost immediately after withdrawal of the drug. The drug is readily absorbed from the gastrointestinal tract following oral administration. At present, HU has an important role as standard of care for treating hyperleukocytosis in chronic and acute myeloid leukemia.

Valproic acid (VPA) has been used clinically as an anticonvulsant and mood-stabilizing drug. During the last two decades, VPA has been described as a histone deacetylase (HDAC) inhibitor and gained increased interest for use in cancer therapy. VPA is administered orally with available routine measurements of serum levels and has a low toxicity profile.

In 1953, 6-MP was an approved antileukemic agent resulting in remissions in children with acute lymphocytic leukemia (ALL). After adding 6-MP to methotrexate and prednisolone in the treatment regimen, the one-year mean survival of children with ALL was increased from 29% to 50%. 6-MP, even about 70 years after its discovery, remains the standard maintenance therapy once the children are in complete remission.