Table 1 Selected prospective studies using diffirent azacitidine administration schedules in myelodysplastic syndrome
Regimen(s) studied | Comparator | Type | MDS risk | N | Results | Reference |
|---|---|---|---|---|---|---|
75 mg/m2 × 7 days continuously | None | Phase II | 98% HR, 0% LR | 43 | ORR 49%, CR 15%, median OS 13.3 months | Silverman, et al. [2] (CALGB 8421) |
7–0 | None | Phase II | 50% HR, 16% LR | 67 | ORR 52%, CR 17% | Silverman, et al. [3] (CALGB 8921) |
7–0 | BSC | Phase III | 46% HR, 54% LR | 191 | ORR 60%; OS: AZA 20 months vs. BSC 14 months, p = 0.10 (53% of BSC group crossed over to receive AZA) | Silverman, et al. [5] |
7–0 | CCR | Phase III | 100% HR | 358 | ORR 49%; CR 17%; OS: AZA 24.5 months AZA vs. CCR 15 months, HR 0.58 (95%CI 0.43–0.77, p = 0.0001) | Fenaux, et al. [4] (AZA-001) |
5–2-2 vs. 5–2-5* vs. 5–0 | N/A | Phase III | 48% LR, 52% HR | 103 | HI rates of 44%, 45%, and 56%, respectively; TI rates of 50%, 55%, and 64%, respectively; CR and OS not assessed | Lyons, et al. [10] |
7–0 | N/A | Phase II | 59% HR, 41% LR | 22 | ORR 27%, CR 27%, OS not assessed | Martin, et al. [37] |
50 mg/m2/d × 10 days | AZA + entinostat 4 mg/m2/d day 3 + day 10 | Phase II | 45% HR, 18% LR | 97 | ORR 46% on AZA only arm, including unilineage HI; CR 12%; median OS 18 months | Prebet, et al. [27] (E1905) |
CC-486 (oral AZA) 120-600 mg daily | None | Phase I | 48% HR, 48% LR | 29 | ORR 73% and CR 40% for treatment-naïve, ORR 35% and CR 0% for previously-treated (including CMML) | Garcia-Manero, et al. [29] |
5–2-2 | N/A | Prospective, observational | 100% HR | 38 | ORR 47%, CR 18%, median OS 16.4 months | Breccia, et al. [33] |
5–2-2 | N/A | Prospective, observational | 100% HR | 60 | ORR 63%, CR 25%, median OS 17 months | Breccia et al. [34] |
5–0 | N/A | Phase II | 100% LR | 32 | ORR 47% on intention-to-treat, CR 19%, median OS 28.5 months | Fil, et al. [35] |
5–0 | N/A | Phase II | 100% LR | 30 | ORR 20% (included possible ESA use), CR not reported, median OS not reached | Tobbiason, et al. [38] |
CC-486 (oral AZA) 300 mg daily × 14 days or 21 days | N/A | Phase I/II | 100% LR (27% by IPSS-R) | 55 | 14-day arm: ORR 36%, CR 14%; 21-day arm: OR 41%, CR 0%; OS not assessed | Garcia-Manero, et al. [30] |
75 mg/m2 × 3 days | Decitabine 20 mg/m2 × 3 days | Phase II | 100% LR (20% HR by IPSS-R) | 40 | ORR 49%, CR 36%, median OS not reached | Jabbour, et al. [32] |