Table 3 Combination of histone deacetylase (HDAC) inhibition and demethylating agents: summary of clinical studies

Raffoux et al., 2010 [64]

65

72

AML (85%) or high-risk MDS

5-AZA 75 mg/m². VPA 35 to 50 mg/kg po day 1 to 7. ATRA 45 mg/m² po day 8 to 28. Six cycles.

After six cycles, 34 patients survived: 13 patients (38%) CR, two patients (6%) PR and 14 patients (41%) had stable disease. Median OS was 12.4 months.

Confusion 33 events, infection 76 events.

Blum et al., 2007 [63]

25

70

AML

Decitabine 15 to 20 mg/m²/d iv days 1 to 10 every 28 days. VPA 15 to 20 mg/kg days 5 to 21 in ten patients.

Response rate was 44%: four patients CR, four patients CRi and three patients PR (AML criteria). Survival not reported.

Neutropenic fever (64%), fatigue and infection (both 48%) were most common.

Soriano et al., 2007 [65]

53

69

AML (92%) or high-risk MDS

5-AZA 75 mg/m²/d. VPA 50 to 75 mg/kg/d days 1 to 7. ATRA 45 mg/m² days 3 to 5. Treatment repeated every 3 weeks.

Overall response rate was 42%: 12 patients (22%) CR. Survival not reported.

Two events of grade IV and 11 events of grade III non-hematological toxicity; mainly fatigue or other neurotoxicities.

Garcia-Manero et al., 2006 [66]

54

60

AML (89%) or MDS

Decitabine 15 mg/m²/d iv. VPA 20 to 50 mg/kg days 1 to 10. Treatment repeated every fourth week.

Twelve patients (22%) had responses: 10 patients CR and two patients CRp. OS 6 months (0.6 to 20.2 months).

Fatigue, nausea and diarrhoea were the most common non-hematological toxicities.

Maslak et al., 2006 [67]

10

66.5

AML (80%) or MDS

5-AZA 75 mg/m²/d days 1 to 7. Sodium phenylbutyrate 200 mg/kg/d iv days 8 to 12. Treatment repeated every 21 to 28 days.

Three patients (30%) PR and two patients (20%) had stable disease. Duration of response was 45 days (37 to 136 days). Survival not reported.

Three patients had neutropenic fever. Nausea, dizziness and fatigue were common.