Azacitidine: A novel agent for myelodysplastic syndromes

Purpose. The pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and safety of azacitidine are reviewed. Summary. Azacitidine is the first drug in a new class of compounds, known as DNA hypomethylating agents, to receive FDA-approved labeling for the treatment of myelodysplastic syndromes. It exerts its antineoplastic activity by causing a direct cytotoxic effect on abnormally proliferating hematopoietic cell lines by interfering with nucleic acid metabolism. Azacitidine is rapidly absorbed following subcutaneous injection, with peak plasma concentrations achieved within 30 minutes of administration. Based on promising results in Phase I-II testing, azacitidine entered Phase III testing in all subtypes of myelodysplastic syndromes. Azacitidine was compared with best supportive care, the previous standard therapy for myelodysplastic syndromes, demonstrating improvements in hematologic response, delaying time to progression to acute myelogenous leukemia, and increasing overall survival. Azacitidine is available as sterile lyophilized powder in single-use vials for reconstitution. The recommended dosage of azacitidine for the first treatment cycle is 75 mg/m² daily for seven days. The treatment cycle should be repeated every four weeks for a minimum of four cycles. Overall, azacitidine appears to be well tolerated, with the most common adverse effects being myelosuppression, nausea, and vomiting. Conclusion. Azacitidine is the first DNA hypomethylating agent approved by FDA for the treatment of myelodysplastic syndromes and has demonstrated superior efficacy and improvements in patients' quality of life and bone marrow function over supportive care.