Table 1.
Recent decitabine trials in the treatment of myelodysplastic syndromes (MDS)
| Trial | No. pts | Phase | Design | Study focus | Results | Dosing | Median no courses | Time to AML progression | Median survival time |
|---|---|---|---|---|---|---|---|---|---|
| Kantarjian et al9 | 170 | III | Randomized, multi-institutional | ORR and time to AML transformation or death | ORR 17%; CR 9% (P < 0.001); PR 8%; HI 13% | 15 mg/m2 IV over 3 h every 8 h for 3 d; total 135 mg/m2 per course repeated every 6 wks | 3 | Compared to BSC: Overall, 12.1 mos vs 7.8 mos (P = 0.16). IPSS Int-2/ high-risk disease, 12.0 mos vs 6.8 mos (P = 0.03). De novo disease, 12.6 mos vs 9.4 mos (P = 0.04). | Compared to BSC: 14.0 mos vs 14.9 mos (P = 0.636) |
| Ruter et al29 | 22 | Three Phase II trials | Pooled | Low dose DAC as retreatment at time of disease recurrence | OR 45%; CR 4.5%; PR 9.1%; HI 31.8% | 15 mg/m2 IV over 4 h given 3 times/d for 3 d Total 135 mg/m2 per course repeated every 6 wks | 3 additional courses | 27.5 mos from time of initial treatment with DAC | |
| Kantarjian et al26 | 115 | II | Single center | Prognostic factors associated with outcome | OR 70%; CR 35%; PR 2%; bone marrow CR with or without HI 23%; other HI 10% | Either, (1) 20 mg/m2 IV × 5 d; (2) 20 mg/m2 subq × 5 d; (3) 10 mg/m2 IV × 10 d Total 100 mg/m2 per course every 4 wks | ≥7 | Not reached | 22 mos |
| Kantarjian et al25 | 95 | II | Randomized, single center | Optimal dosage of decitabine | Overall: OR 73%; CR 34%; PR 1%; marrow CR with or without HI 24%; HI 14% 5 d IV schedule, CR 39% (P < 0.05) | Either, (1) 20 mg/m2 IV × 5 d; (2) 20 mg/m2 subq × 5 d; (3) 10 mg/m2 IV × 10 d | 6+ | 27% over 18 mos | 19 mos |
| Kantarjian et al23 | Group A (115) and group B (376) | II | Historical comparison at single center Group A: subcohort of matched pts by age, IPSS, and cytogenetics Group B: entire cohort without matching | Compare long term results of lower intensity chemo (ie, DAC) with results from AML-type intensive chemo in higher risk MDS | CR 43% compared to 46% with intensive chemo in Group A, and 52% in Group B. Compared with Group A, mortality at 6 wks was 3% with DAC vs 13% with intensive chemo (P = 0.006); and at 3 mos 7% with DAC vs 23% with intensive chemo (P = 0.001) | Either, (1) 20 mg/m2 IV over 1 h × 5 d; (2) 20 mg/m2 subq in 2 doses daily; (3) 10 mg/m2 IV over 1 h × 10 d Total 100 mg/m2 per course | Compared to intensive chemo, pts in Group A had 22 mos vs 12 mos (P < 0.001) | ||
| Borthakur et al46 | 14 | II | Early results | Efficacy of DAC after failure on AZA | ORR 28%; CR 21%; marrow CR with HI 7% | 20 mg/m2 IV over 1 h × 5 d every 4 wks | 3 | 4 mos | 6 mos |
| Steensma et al28 | 99 | II | Multicenter, nonrandomized, and open-label | Efficacy and safety of an outpatient DAC regimen | ORR 32%, overall improvement rate 51%, CR 17%, HI 18% | 20 mg/m2 IV once daily over 1 h × 5 d every 4 wks | 5 | 19.4 mos |
Abbreviations: AZA, 5-azacitidine; AML, acute myeloid leukemia; BSC, best supportive care; CR, complete remission; DAC, decitabine; HI, hematologic improvement; IPSS, International Prognostic Scoring System; IV, intravenous; OR, objective response by modified IWG criteria; mos, months; ORR, overall response rate; PR, partial remission; pts, patients.