10-day decitabine schedule in acute myeloid leukaemia: no extra bang for the buck
Mené sur 71 patients atteints d'une leucémie myéloïde aiguë récemment diagnostiquée, cet essai de phase II évalue l'efficacité, du point de vue de la rémission complète, et la toxicité de cycles de décitabine dispensée sur une durée de 10 jours ou sur une durée de 5 jours (durée de suivi : 38,2 mois)
Decitabine is a cytosine nucleoside analogue that has antileukaemic activity at a remarkably wide range of doses. Most relevant to current clinical practice, decitabine has DNA hypomethylating activity at low doses, leading to gradual responses through re-expression of tumour-suppressor and tumour-differentiation genes. The initial decitabine schedule to obtain approval by the US Food and Drug Administration (FDA) for myelodysplastic syndromes was an inpatient regimen of 15 mg/m 2 every 8 h for 3 days, repeated every 6 weeks. Later studies in myelodysplastic syndromes established the activity of 20 mg/m 2 per day given for 5 days, repeated every 4 weeks, which was also FDA approved and adopted as a more convenient outpatient treatment schedule. In a phase 2 trial of older patients with untreated acute myeloid leukaemia, the 5-day decitabine regimen led to complete response in 13 (24%) of 55 patients and median overall survival of 7·7 months. This regimen was subsequently compared with low-dose cytarabine or supportive care in a phase 3 trial of 485 older patients with previously untreated acute myeloid leukaemia. Complete response was higher with decitabine (18% vs 8%), but a survival benefit was only seen in an unplanned analysis after longer follow-up.
The Lancet Haematology , résumé, 2017