Results of the Initial Treatment Phase of a Study of Three Alternative Dosing Schedules of Azacitidine (Vidaza®) in Patients with Myelodysplastic Syndromes (MDS).

Background: Azacitidine (Vidaza®) is an effective and safe treatment (Tx) for patients (pts) with MDS (

Methods: In this phase II multicenter, open-label trial, MDS pts were randomized to 1 of 3 regimens administered every 4 weeks for 6 cycles: AZA 5-2-2 (75 mg/m²/day x 5 days, followed by 2 days no Tx, followed by 75 mg/m²/day x 2 days); AZA 5-2-5 (50 mg/m²/day x 5 days, followed by 2 days no Tx, followed by 50 mg/m²/day x 5 days); or AZA 5 (75 mg/m²/day x 5 days). Major and minor hematologic improvements (HI) were assessed by International Working Group (IWG) criteria (

Results: A total of 151 pts were randomized to Tx with AZA 5-2-2 (n=50), AZA 5-2-5 (n=51), or AZA 5 (n=50). Most pts are FAB classification RA/RARS (57%) or RAEB (30%). Of the 139 pts (92%) who received ≥56 days of Tx and are IWG evaluable, 74 pts (49%) completed ≥6 Tx cycles. The median number of Tx cycles across all Tx arms was 6. Of IWG-evaluable pts, 71 (51%) experienced HI (Table). The proportions of red blood cell (RBC) transfusion-dependent pts who achieved transfusion independence were AZA 5-2-2: 55% (12/22), AZA 5-2-5: 60% (12/20), and AZA-5: 67% (16/24). In FAB low-risk (RA/RARS) transfusion-dependent pts at baseline, RBC transfusion independence was reached by 60% (9/15), 56% (5/9), and 61% (11/18), respectively. No Tx-related mortality has been reported. Most grades 3 and 4 Tx-related AEs were hematological (AZA 5-2-2: 44%, AZA 5-2-5: 33%, AZA 5: 18%).

Conclusions: Independent of the alternative dosing regimen, the results of the initial 6-cycle Tx phase demonstrate a consistent response for HI, RBC transfusion independence, and safety profile across a broad range of MDS pts, including FAB low-risk pts. These results appear similar to those with the approved FDA regimen and further support the benefit of azacitidine in pts who are transfusion-dependent. Eligible pts continue to receive Tx during the ongoing 12-month maintenance phase of the study.