BioMed Research International / 2011 / Article / Tab 4

Review Article

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)SchedulePatient numberDiagnosis: patient numberResponse [%]Toxicity
DNMTiHDACiOverallCRCRpPROthers

Garcia-Manero et al. (2006) [144]DAC 15 mg/m2 days 1–10+VA orally 20, 35, 50 mg/kg (days 1–10)54AML: MDS: 12 (22%)10 (19%)2 (3%)CNS toxicity
Soriano et al. (2007) [146]AZA 75 mg/m2 day 1–7+VA orally 50, 62, 5 and 75 mg/kg (days 1–7) + ATRA 45 mg/m2/ day (days 3–7)53AML: MDS: 22 (41%)12 (22%)3 (5%)7 (13%) BM responsesCNS toxicity
Maslak et al. (2007) [147]AZA 75 mg/m2 days 1–7+PB 200 mg/kg for 5 days after AZA10AML: MDS: 3 (30%)3 (30%)CNS toxicity, fever, nausea, fatigue
Blum et al. (2007) [145]DAC 20 mg/m2 days 1–10+VA escalating doses (days 5–21) 15, 20 or 25 mg/kg11AML: 6 (54%)2 (18%)2 (18%)2 (18%)CRiCNS toxicity, myelosuppre ssion, infection, myeloid differentiation syndrome
Gore et al. (2006) [143]AZA 50 mg/m2 days 1–14, 1–10 or 1–5; 75 mg/m2 days 1–5; 25 mg/m2 day 1–14+PB 375 mg/kg/day for 7 days after AZA32AML: MDS: CMML: 11 (38%)4 (14%)1 (3%)6 (21%) HICNS 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.