Skip to main content

Advertisement

Table 1 Selected prospective studies using diffirent azacitidine administration schedules in myelodysplastic syndrome

From: More is less, less is more, or does it really matter? The curious case of impact of azacitidine administration schedules on outcomes in patients with myelodysplastic syndromes

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]
  1. Abbreviations: AZA Azacitidine, BSC Best supportive care, CCR Conventional care regimen, CI Confidence interval, CMML Chronic myelomonocytic leukemia, CR Complete response, HI Hematological improvement, HR Higher-risk, LR Lower-risk, ORR Overall response rate, OS Overall survival, RCT Randomized controlled trial, SD Stable disease, TI Transfusion-independence
  2. *5–2-5: azacitidine 50 mg/m2 daily subcutaneously for 5 days, then 2 days without therapy, then 50 mg/m2 daily subcutaneously for 5 days