Previous CALGB trials published by Silverman et al (

JCO
2002
;
20
:
2429
) have shown azacitidine to be efficacious and well tolerated in the treatment of MDS at a dosing schedule of 75 mg/m2/day x 7 days every 28 days. The objective of this phase II, multicenter, randomized, open-label trial was to study treatment response in patients with MDS with 3 alternative, subcutaneous azacitidine dosing regimens, each eliminating the need for weekend injections. The 3 alternative dosing schedules, repeated in 28-day cycles, were AZA 5-2-2 (75 mg/m2/day x 5 days, followed by 2 days of no treatment, followed by 75 mg/m2/day x 2 days), AZA 5-2-5 (50 mg/m2/day x 5 days, followed by 2 days of no treatment, followed by 50 mg/m2/day x 5 days), and AZA 5 (75 mg/m2/day x 5 days). Eligible MDS patients must have had a life expectancy of ≥ 7 months and an ECOG performance status grade of 0–3, with a FAB classification of RA, RARS, RAEB, RAEB-T, or CMML. RA and RARS patients must also have had either hemoglobin < 110 g/L with transfusion requirements, a platelet count < 100 x 109/L, or an ANC < 1.5 x 109/L. Patients experiencing International Working Group response criteria for MDS (
Blood
2000
;
96
:
3671
) defined as complete remission, partial remission, stable disease, or hematologic improvement (major or minor) after 6 cycles of treatment were eligible to receive an additional 12 cycles. A total of 44 patients have been randomized to date with 22, 14, and 8 receiving either AZA 5-2-2, AZA 5-2-5, or AZA 5, respectively. As the AZA 5 day dosing schedule was added later to the protocol by amendment, no patients in this arm are currently evaluable for response. Most patients are male (64%) and elderly with a median age of 74 years. Most patients have RA, using either FAB (45%) or WHO (36%) definitions; another 27% and 16% have RAEB or RAEB-1, respectively. As azacitidine is incorporated into DNA/RNA through successive cell cycles, patients often require a minimum of 4 to 6 cycles of azacitidine before responses are observed. Early results show that the efficacy and tolerability observed with the alternative dosing schedules are consistent with the 75 mg/m2/day x 7 days dosing results from previous studies.

Topics:
azacitidine, myelodysplastic syndrome, refractory anemia with excess blasts, refractory anemia with sideroblasts, complete remission, dna, electrocorticogram, hemoglobin, leukemia, myelomonocytic, chronic, partial response

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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