General Information

Vidaza (azacitidine) is an anti-neoplastic pyrimidine nucleoside analog used to treat several subtypes of myelodysplastic syndrome, diseases caused by abnormalities in the blood-forming cells of the bone marrow that result in underproduction of healthy blood cells. The drug exerts a cytotoxic effect on rapidly dividing cells, including cancerous cells, and may help restore normal function to genes controlling proper cellular differentiation and proliferation.

Vidaza is specifically indicated for the treatment of the following myelodysplastic syndrome subtypes:

• Refractory anemia
• Refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions)
• Refractory anemia with excess blasts
• Refractory anemia with excess blasts in transformation
• Chronic myelomonocytic leukemia

Mechanism of Action

Azacitidine utilizes a dual mechanism of action, causing the hypomethylation of DNA and exerting direct cytotoxic in abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore normal gene function to genes controlling cellular division and differentiation (the genes presumed to be abnormal or nonfunctional in myelodysplastic syndromes). Cytotoxic effects cause the death of rapidly dividing abnormal cells. Vidaza is not strongly active in non-proliferating cells, limiting toxicity to that resulting from affected tissues.

Side Effects

Adverse events associated with the use of Vidaza may include (but are not limited to) the following:

• Thrombocytopenia
• Neutropenia
• Nausea
• Vomiting
• Anorexia
• Arthalgia
• Injection site erythema
• Injection site pain

Additionally, animal models have demostrated teratogenic potential in both men and women, and embryotoxicity during pregnancy.

Dosing/Administration

Vidaza is administered via subcutaneous injection, with a starting dosing regimen of 75 mg/m2 daily for seven days, every four weeks. The dose may be increased to 100 mg/m2 if the initial dose is insufficient and toxicity was manageable.

Clinical Trial Results

FDA approval of Vidaza was based on a randomized, open-label, controlled trial that enrolled 191 patients (172 evaluable) with any of the five subtypes of myelodysplastic syndrome noted above. Subjects were randomized to receive either subcutaneous Vidaza plus supportive care (n=99) or supportive care alone (n=92); subjects in the supportive care arm were free to cross over to the Vidaza arm if their symptoms worsened during the trial. Vidaza was administered via subcutaneous injection at 75 mg/m2 daily for seven days every four weeks; the dose was increased to 100 mg/m2 if no beneficial effect was seen after two treatment cycles. The drug was seen to produce a statistically significant response in 15.7 percent (n=14 of 89) of evaluable subjects in the Vidaza arm, and 12.8 percent (n=6 of 47) of the crossover group. Of the Vidaza-arm subjects exhibiting a response, five of the 14 showed a complete response and nine of the 14 showed a partial response. Additional studies yielded consistent results. Furthermore, an additional 24 percent of subjects who did not meet partial response criteria were considered "improved," and two-thirds were no longer transfusion dependent.