[819] Results of the Initial Treatment Phase of a Study of Three Alternative Dosing Schedules of Azacitidine (Vidaza
) in Patients with Myelodysplastic Syndromes (MDS). Session Type: Oral Session
Roger M. Lyons, Thomas Cosgriff, Sanjiv Modi, Heidi McIntyre, Indra Fernando, Jay Backstrom, C.L. Beach Cancer Care Centers of South Texas, San Antonio, TX, USA; Hematology and Oncology Specialists, New Orleans, LA, USA; Joliet Oncology-Hematology Associates, Ltd, Joliet, IL, USA; Pharmion Corporation, Overland Park, KS, USA
Background: Azacitidine (Vidaza) is an effective and safe treatment (Tx) for patients (pts) with MDS (JCO 2002;20:2429) at a dosing schedule of 75 mg/m
/day SC for 7 days every 4 weeks. A dosing schedule eliminating the need for weekend administration would be more convenient to pts and clinicians. Reported here are results of the recently completed initial Tx phase (6 cycles of randomized Tx) of an ongoing study evaluating 3 alternative azacitidine dosing schedules. 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/m/day x 5 days, followed by 2 days no Tx, followed by 75 mg/m/day x 2 days); AZA 5-2-5 (50 mg/m/day x 5 days, followed by 2 days no Tx, followed by 50 mg/m/day x 5 days); or AZA 5 (75 mg/m/day x 5 days). Major and minor hematologic improvements (HI) were assessed by International Working Group (IWG) criteria (Blood 2000;96:3671) and pts with 
56 Tx days were IWG evaluable. To determine whether therapeutic response is maintained after 6 cycles, a 12-month maintenance phase using the AZA-5 regimen administered every 4 or 6 weeks was added, and pts with at least stable disease were eligible to participate in that phase of the study. 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.
| Major HI | AZA 5-2-2 (N=46) | AZA 5-2-5 (N=44) | AZA 5 (N=49) |
| n (%) (95% CI) | n (%) (95% CI) | n (%) (95% CI) | |
| Erythroid | 15 (33) (20, 48) | 17 (39) (24, 55) | 19 (39) (25, 54) |
| Platelet | 10 (22) (11, 36) | 8 (18) (8, 33) | 9 (18) (9, 32) |
| Neutrophil | 3 (7) (29, 100) | 4 (9) (40, 100) | 4 (8) (40, 100) |
| Any HI* | 20 (44) (29, 59) | 23 (52) (37, 68) | 28 (57) (42, 71) |
Abstract #819 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Hypomethylation|Regimen|Clinical Trial
Disclosure: Employment: H. McIntyre, I. Fernando, J. Backstrom, and C.L. Beach are employees of Pharmion Corporation. Consultancy: R. Lyons. Ownership Interests:; H. McIntyre, I. Fernando, J. Backstrom, and C.L. Beach. Research Funding: R. Lyons: study only. Honoraria Information: T. Cosgriff: honorarium for Vidaza workshop in 2006, Las Vegas NV, Membership Information: R. Lyons: Pharmion advisory committee. Off Label Use: Yes, dosing regimens are different from the approved prescribing information.
Tuesday, December 11, 2007 8:00 AM
Session Info: Simultaneous Session: Myelodysplastic Syndromes: Advances in Therapeutic Options (7:30 a.m.-9:00 a.m.)