BioMed Research International / 2011 / Article / Tab 3

Review Article

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 substancePhaseSchedulePatient numberDiagnosis: patient numberResponses
(i) overall [%]
(ii) details
Toxicity

Gore et al. (2001) [127]PhenylbutyrateIi.v., 125–500 mg/kg/day 7/28 days continuous infusion27MDS: , AML: 8 [30%]
4 HI, 4 decline of PB blasts
CNS toxicity, hypocalcemia, nausea/vomiting
Gore et al. (2002) [128]PhenylbutyrateIi.v., 375 mg/kg/day 7/14 or 21/28 days cont. infusion23MDS: , AML: 2 [9%]
2 HI (21/28 schedule)
CNS toxicity, skin reaction, hypo-calcemia
Zhou et al. (2002) [129]Phenylbutyrate + ATRAIi.v., 200–400 mg/kg/day 25 days5AML M3: 1 [20%]
1 RT-PCR neg. CR
Transient CNS depression
Odenike et al. (2006) [130]DepsipeptideIIi.v., 18 mg/m2/dayday 1, 8 and 15 every 28 days18AML: 2 [11%]
2 BM- blast clearance (t(8;21) and t(4;21))
Nausea, vomiting, fatigue
Byrd et al. (2005) [131]DepsipeptideIi.v., 13 mg/m2 day 1, 8, 15 every 28 days10AML: Transient declines in PB and BM blastsFatigue, vomiting, nausea, tumor lysis syndrome, diarrhea
Giles et al. (2006) [132]LBH589Ii.v., 4.8–14 mg/m2, days 1–7 every 21 days14AML: , MDS: 8 [57%]
8 patients transient decline in PB blasts
QT-prolongation, nausea, vomiting, hypokalemia
Garcia-Manero et al. (2005) [133]Vorinostat (SAHA)IOral, 100–300 mg 2-3 ×/day, 14/21 days35AML: , MDS: , CML: 9 [25%]
1CR, 2CRp, 1PR, 5 complete marrow responses
Nausea, vomiting, diarrhea, neutropenia, typhlitis, fatigue
Gojo et al. (2007) [134]MS-275IOral, 4–10 mg/m2, 1 ×week for 2 or 4 weeks38AML: 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.