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

Table 3

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

Author (year)	HDACi substance	Phase	Schedule	Patient number	Diagnosis: patient number	Responses; (i) overall [%]; (ii) details	Toxicity
Gore et al. (2001) [127]	Phenylbutyrate	I	i.v., 125–500 mg/kg/day 7/28 days continuous infusion	27	MDS: 𝑛=11, AML: 𝑛=16	8 [30%]; 4 HI, 4 decline of PB blasts	CNS toxicity, hypocalcemia, nausea/vomiting
Gore et al. (2002) [128]	Phenylbutyrate	I	i.v., 375 mg/kg/day 7/14 or 21/28 days cont. infusion	23	MDS: 𝑛=9, AML: 𝑛=14	2 [9%]; 2 HI (21/28 schedule)	CNS toxicity, skin reaction, hypo-calcemia
Zhou et al. (2002) [129]	Phenylbutyrate + ATRA	I	i.v., 200–400 mg/kg/day 25 days	5	AML M3: 𝑛=5	1 [20%]; 1 RT-PCR neg. CR	Transient CNS depression
Odenike et al. (2006) [130]	Depsipeptide	II	i.v., 18 mg/m^2/dayday 1, 8 and 15 every 28 days	18	AML: 𝑛=18	2 [11%]; 2 BM- blast clearance (t(8;21) and t(4;21))	Nausea, vomiting, fatigue
Byrd et al. (2005) [131]	Depsipeptide	I	i.v., 13 mg/m^2 day 1, 8, 15 every 28 days	10	AML: 𝑛=10	Transient declines in PB and BM blasts	Fatigue, vomiting, nausea, tumor lysis syndrome, diarrhea
Giles et al. (2006) [132]	LBH589	I	i.v., 4.8–14 mg/m^2, days 1–7 every 21 days	14	AML: 𝑛=13, MDS: 𝑛=1	8 [57%]; 8 patients transient decline in PB blasts	QT-prolongation, nausea, vomiting, hypokalemia
Garcia-Manero et al. (2005) [133]	Vorinostat (SAHA)	I	Oral, 100–300 mg 2-3 ×/day, 14/21 days	35	AML: 𝑛=31, MDS: 𝑛=3, CML: 𝑛=1	9 [25%]; 1CR, 2CRp, 1PR, 5 complete marrow responses	Nausea, vomiting, diarrhea, neutropenia, typhlitis, fatigue
Gojo et al. (2007) [134]	MS-275	I	Oral, 4–10 mg/m^2, 1 ×week for 2 or 4 weeks	38	AML: 𝑛=38	7 [18%]; 7 HI, transient decline in PB and BM blasts	CNS toxicity, infections, fatigue, nausea, vomiting

Abbreviations. AML: acute myeloid leukaemia; ATRA: All-trans-Retinoic-Acid; BM: bone marrow CML: chronic myelogenous leukaemia; CNS: central nervous system; CR: complete remission; CRp: complete response with incomplete platelet recovery; HDACi: histone deacetylase inhibitors; HI: haematologic improvement; MDS: myelodysplastic syndrome; PB: peripheral blood; PR: partial response.