, Volume 72, Issue 8, pp 1111-1136
Date: 10 Dec 2012


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Azacitidine (Vidaza®) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties.

The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone.

The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML).

The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS.

Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials, peripheral cytopenias were the most commonly occurring adverse event in azacitidine recipients, with gastrointestinal adverse events (e.g. nausea, vomiting and diarrhoea) and injection-site reactions among the most commonly occurring non-haematological adverse events.

In conclusion, azacitidine is an important agent for use in the treatment of patients with MDS/AML.

Various sections of the manuscript reviewed by: A.T. Fathi, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; G. Huls, Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; L. Maurillo, Chair of Hematology, Tor Vergata Foundation Polyclinic, Rome, Italy; P. Musto, Department of Onco-Hematology, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; T. Prébet, Department of Haematology, Institut Paoli Calmettes, Marseille, France; V. Santini, Haematology SOD, AOU Careggi, University of Florence, Firenze, Italy; T. Uchida, Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘azacitidine’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘azacitidine’ and (‘myelodysplastic syndrome’ or ‘myelodysplastic syndromes’). Searches were last updated 16 April 2012.
Selection: Studies in patients with myelodysplastic syndromes who received azacitidine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Azacitidine, myelodysplastic syndromes, acute myeloid leukaemia, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.