Randomized trial of intermediate-dose cytarabine in induction and consolidation therapy in adults with acute myeloid leukaemia
Mené sur 591 patients atteints d'une leucémie myéloïde aiguë (âge : 15-55 ans), cet essai randomisé compare l'efficacité, du point de vue de la survie sans maladie, de doses intermédiaires et de doses conventionnelles de cytarabine, dispensées en combinaison avec de la daunorubicine et du mépesuccinate d'omacétaxine, en traitement d'induction et de consolidation
Purpose: Cytarabine, 100-200 mg/mE+2/d, is commonly-used in induction therapy of acute myeloid leukaemia (AML). Whether a higher dose of cytarabine would be more effective is unknown. Also, there is controversy whether high-dose cytarabine is better than an intermediate-dose combined with other drugs for post-remission therapy. In this open-label, randomized, parallel controlled group study, roles of intermediate-dose cytarabine were investigated. Subjects and Methods: Subjects with AML age 15-55 years were randomized to receive daunorubicin, omacetaxine mepesuccinate and conventional- or intermediate-dose cytarabine. Subjects achieving complete remission were randomized to receive 3 courses of high-dose cytarabine or 2 courses of intermediate-dose cytarabine with daunorubicin in the 1st and mitoxantrone in the 2nd course. The primary endpoint was disease-free survival (DFS). Results: 591 subjects were randomized to intermediate- (N=295) or conventional-dose (N=296) cytarabine group. Three-year DFSs were 67% (95% confidence interval [CI], 61-73) in the intermediate-dose cohort compared with 54% (95%CI, 48-61) in the conventional-dose cohort (Hazard Ratio [HR]=0.67; 95%CI, 0.51-0.89; P=0.005). Three-year survivals were 68% (95%CI, 63-74) and 59% (95%CI, 53-65; HR=0.720 95%CI, 0.56-0.94; P=0.014). Two course of intermediate-dose cytarabine with daunorubicin or mitoxantrone resulted in similar DFS and survival as three course of high-dose cytarabine when used for post-remission therapy. Conclusions: Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML age 15-55 years compared with conventional-dose cytarabine.