Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Vidaza (Celgene)
vials containing 100 mg as lyophilised powder for reconstitution
Approved indication: myelodysplasia, leukaemia
Australian Medicines Handbook section 14

The myelodysplastic syndromes are disorders in which the pluripotent stem cells function abnormally. As any cell lines can be affected the patient may have anaemia, neutropenia or thrombocytopenia. The syndromes include chronic myelomonocytic leukaemia and the myelodysplasia may progress to acute myeloid leukaemia.

In myelodysplasia, tumour suppressor genes may be inactivated by hypermethylation. Preventing hypermethylation may reduce the proliferation of abnormal cells.

Azacitidine is an analogue of cytidine, one of the nucleosides which make up nucleic acids. When azacitidine is incorporated into DNA it inhibits DNA methyltransferase, reducing hypermethylation, and has a direct cytotoxic effect on abnormally proliferating cells.

In the first treatment cycle azacitidine is given by daily subcutaneous injection for seven days. This cycle is repeated every four weeks for as long as the patient continues to benefit.

Most of the dose is excreted in the urine as azacitidine and its metabolites. Azacitidine is contraindicated in patients with malignant hepatic tumours and those with renal failure.

After phase II trials of intravenous and subcutaneous doses produced favourable results, a phase III trial was carried out in 191 patients with myelodysplasia. These patients were randomly assigned to azacitidine or supportive care. They were assessed after four treatment cycles, and those who had responded to azacitidine could continue. Responses were assessed by changes in the blood and bone marrow and the need for transfusion. In the azacitidine group, 16% of the patients had a partial response and 7% had a complete response. The median duration of all the improvements was 15 months. No-one in the supportive care group had a complete or a partial response. With supportive care, the median time to death or the development of acute leukaemia was 12 months, compared with 21 months in the patients treated with azacitidine.1

Data from this trial and the phase II trials were reanalysed when an application was made to market the drug in the USA. The assessment criteria had changed and the reanalysis showed that few patients had partial remissions, but 10-17% had complete remissions and 23-36% had some haematological improvement. Under the new criteria some patients were found to have had acute myeloid leukaemia at the start of the studies. Those treated with azacitidine had a median survival of 19.3 months compared with 12.9 months for supportive care.2

Another study compared azacitidine with conventional care which could include chemotherapy. This study randomised 358 patients with myelodysplastic syndromes including chronic myelomonocytic leukaemia. Acute myeloid leukaemia developed after a median of 17.8 months with azacitidine and 11.5 months with conventional care. The patients had a median survival of 24.5 months with azacitidine and 15 months with conventional care. However, only 25 patients in the conventional care group received intensive chemotherapy and their survival rate was not statistically different from that of the azacitidine group. Patients given azacitidine had higher haemoglobin concentrations so there was a reduced need for red blood cell transfusions. The approved indications for azacitidine are based on this trial. These are specified forms of myelodysplastic syndromes, chronic myelomonocytic leukaemia, and acute myeloid leukaemia, when allogenic stem cell transplant is not indicated.3

Although azacitidine may reduce transfusion requirements it is a cytotoxic drug so patients still need to be monitored for anaemia, neutropenia and thrombocytopenia, particularly at the start of treatment. Infections are common and some patients will develop febrile neutropenia. In addition to full blood counts the patient's liver and renal function should be regularly checked because of the risk of toxicity. As gastrointestinal problems are frequent, antiemetic drugs should be given before each treatment. Other frequent adverse reactions include injection site reactions, dyspnoea, anorexia, arthralgia, dizziness and bruising. Despite the wide range of potentially severe adverse effects, there is evidence that azacitidine leads to a better quality of life by improving the patient's physical functioning, fatigue and dyspnoea.1

Most of the patients with myelodysplastic syndromes are elderly. They are not usually suitable for stem cell transplantation, so management has involved supportive care. Azacitidine seems to offer improved survival to specific groups of these patients.

Read about The Transparency Score manufacturer provided additional useful information

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (


  1. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429-40.
  2. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429-40.
  3. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009;10:223-32.