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

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2005, The American Society of Hematology
2005
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