A cytosine analog that incorporates into DNA and traps and depletes DNA methyltransferase enzymes, leading to loss of DNA methylation and gene reactivation.
A S-phase cell cycle sensitive drug since it is required to incorporate into DNA for activity.
Can reactivate and express silenced genes, such as tumor suppressor genes.
Does not inhibit progression of cells from G1 into S phase slowing progression of cells through the cell cycle.
Decitabine is a nucleoside metabolic inhibitor that is believed to exert its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis.
A hypomethylating agent with activity in myelodysplastic syndrome, acute myelogenous leukemia and chronic myelogenous leukemia.
May require prolonged administration to achieve maximum benefit in MDS.
Phase II studies in myelodysplastic syndromes overall response rates of 42-54% and complete response rates of 20-28%.
Complete remission rate of 10-20% when given as a 150 mg/M2 continuous infusion in MDS.
Multiple dose levels are effective.
Optimal doses in MDS 20 mg/m2 intravenously over 1 hour for 5 days every 4 weeks.
Low dose of 15 mg/m2 three times daily for three days is effective in MDS.
Has activity in sickle cell anemia.
0.15 mg/kg daily for 10 days efficacious in reactivating fetal hemoglobin in sickle cell disease.