Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia

Azacitidine (Vidaza, Celgene) is an anticancer drug that is thought to work by re-establishing cells' natural mechanisms to control abnormal growth. Azacitidine has a UK marketing authorisation for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:

• intermediate-2 and high-risk myelodysplastic syndromes according to the International Prognostic Scoring System (IPSS)

• chronic myelomonocytic leukaemia with 10% to 29% marrow blasts without myeloproliferative disorder or

• acute myeloid leukaemia with 20% to 30% blasts and multilineage dysplasia, according to World Health Organization classification.

Azacitidine is contraindicated in patients who have known hypersensitivity to azacitidine or to any of its excipients; in women who are breastfeeding; and in patients with advanced malignant hepatic tumours. The summary of product characteristics (SPC) states that complete blood counts should be performed before starting therapy, and as often as needed, to monitor response and toxicity. The SPC lists precautions for use in patients with liver or kidney impairment, and cardiac or pulmonary disease. The SPC reports that the most common adverse reactions are thrombocytopenia, neutropenia, leukopenia, nausea, vomiting and injection site reactions. For full details of side effects and contraindications, see the SPC.

Azacitidine is injected subcutaneously daily for 7 days, followed by a rest period of 21 days. The SPC states that patients should be treated for a minimum of 6 cycles. The recommended dose is 75 mg/m² of body surface area. The SPC states that patients should be pre-medicated with anti-emetics to prevent nausea and vomiting. The list price of azacitidine is £321 for a 100-mg vial (excluding VAT; BNF, edition 60). Based on a body surface area of 1.7 m² and a dose of 75 mg/m², 14 vials would be required for 1 cycle (2 vials for each day of treatment). Costs may vary in different settings because of negotiated procurement discounts.

The manufacturer had agreed a patient access scheme with the Department of Health in which azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia would be available with a discount applied to all invoices (referred to as the 'original' patient access scheme in this document). The manufacturer subsequently proposed a revised patient access scheme, in which the discount level is revised and is commercial-in-confidence. The Department of Health has agreed that the revised patient access scheme can be included in this appraisal in January 2011. The manufacturer has agreed that the revised patient access scheme will remain in place until the publication of reviewed NICE guidance.