The drug azacitidine dramatically improves the survival of patients who have high-risk forms of myelodysplastic syndromes (MDS), according to an Article published Online First and in the March issue of The Lancet Oncology .
MDS are a diverse group of bone-marrow disorders that frequently develop into acute myeloid leukaemia (AML). Besides bone-marrow transplantation, which is suitable for only a small proportion of patients, no other existing treatments provide a notable survival benefit for patients with higher-risk MDS.
In a large, multicentre, international phase III trial, Prof Pierre Fenaux of the Université Paris XIII, France, and colleagues assessed 358 patients with higher-risk MDS. 179 patients were randomly assigned to receive azacitidine injections for 7 days of each month, for at least 6 months; the remaining 179 patients were randomly allocated to one of the most commonly used conventional care regimens—best supportive care, low-doses of cytarabine, or classical intensive chemotherapy with an anthracycline and cytarabine—at their clinician's discretion. Patients were followed up for a median of 21•1 months.
Overall survival was more than 9 months longer in patients treated with azacitidine than in patients who received conventional care (median 24•5 months vs 15 months); the survival benefit in the azacitidine group was seen after only 3 months of treatment. The researchers estimate that at 2 years after the start of treatment, twice as many patients on azacitidine as those receiving conventional care would still be alive.
Additionally, azacitidine treatment delayed progression to AML by 6 months (17•8 months to progression in the azacitidine group vs 11•5 months in the conventional care group); patients receiving azacitidine were also significantly more likely to undergo complete or partial remission than were those who received conventional care.
The frequency of severe blood-related side-effects was slightly higher in patients who received azacitidine than in patients who received best supportive care, but lower than in patients who received chemotherapy; additionally, the number of bleeding-related complications with azacitidine was similar to that with conventional care. There was a slightly lower rate of infections in the azacitidine group than in the conventional care group.
Prof Fenaux says that: "The results of this study indicate that azacitidine significantly lengthens overall survival and changes the natural history of MDS in patients with higher-risk disease"; azacitidine should, therefore, become the reference treatment in most patients with this condition. The authors also suggest, however, that: "intensive chemotherapy may remain the appropriate treatment in some situations in higher-risk MDS, especially before allogeneic stem-cell transplantation in candidates for this procedure who have an excess of marrow blasts."
Prof Pierre Fenaux, Hopital Avicenne/Université Paris 13, Bobigny, France T) +44(0)1489557051/7050 E) pierre.fenaux@avc.aphp.fr
For full Article, see: http://press.thelancet.com/TLOpreleuk.pdf
NOTES FOR EDITOR
The Lancet Oncology