Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?

Table 4

Clinical trials of combination regimen with DNMTi and HDACi (adapted and extended from [15, 17]; see also current and ongoing clinical trials at http://www.clinicaltrials.gov/).

Author (year)	Schedule		Patient number	Diagnosis: patient number	Response 𝑛 [%]					Toxicity
	DNMTi	HDACi			Overall	CR	CRp	PR	Others
Garcia-Manero et al. (2006) [144]	DAC 15 mg/m^2 days 1–10+	VA orally 20, 35, 50 mg/kg (days 1–10)	54	AML: 𝑛=48 MDS: 𝑛=6	12 (22%)	10 (19%)	2 (3%)			CNS toxicity
Soriano et al. (2007) [146]	AZA 75 mg/m^2 day 1–7+	VA orally 50, 62, 5 and 75 mg/kg (days 1–7) + ATRA 45 mg/m^2/ day (days 3–7)	53	AML: 𝑛=49 MDS: 𝑛=4	22 (41%)	12 (22%)	3 (5%)		7 (13%) BM responses	CNS toxicity
Maslak et al. (2007) [147]	AZA 75 mg/m^2 days 1–7+	PB 200 mg/kg for 5 days after AZA	10	AML: 𝑛=8 MDS: 𝑛=2	3 (30%)			3 (30%)		CNS toxicity, fever, nausea, fatigue
Blum et al. (2007) [145]	DAC 20 mg/m^2 days 1–10+	VA escalating doses (days 5–21) 15, 20 or 25 mg/kg	11	AML: 𝑛=11	6 (54%)	2 (18%)		2 (18%)	2 (18%)CRi	CNS toxicity, myelosuppre ssion, infection, myeloid differentiation syndrome
Gore et al. (2006) [143]	AZA 50 mg/m^2 days 1–14, 1–10 or 1–5; 75 mg/m^2 days 1–5; 25 mg/m^2 day 1–14+	PB 375 mg/kg/day for 7 days after AZA	32	AML: 𝑛=18 MDS: 𝑛=13 CMML: 𝑛=1	11 (38%)	4 (14%)		1 (3%)	6 (21%) HI	CNS toxicity, mild nausea, injection sidereactions, asthenia, myelosuppression

Abbreviations. AML: acute myeloid leukaemia; ATRA: all-trans-Retinoic-Acid; AZA: azazytidine; CMML: chronic myelomonocytic leukaemia; CNS: central nervous system; CR: complete remission; CRi: complete responses with incomplete blood count recovery; CRp: complete response with incomplete platelet recovery; DAC: decitabine; DNMTi: DNA methyl transferase inhibitors; HDACi: histone deacetylase inhibitors; HI: haematologic improvement; MDS: myelodysplastic syndrome; PB: phenylbutyrate; VA: valproic acid.