| DNMT Inhibiotors |
Azacytidine |
Hematological side-effects, gastrointestinal toxicity, erythema (Christman 2002Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002; 21(35): 5483-5495.) |
|
Decitabine |
Myelosuppression, gastrointestinal toxicity (Derissen et al. 2013Derissen EJ, Beijnen JH and Schellens JH. Concise drug review: azacitidine and decitabine. The oncologist. 2013; 18(5): 619-624.) |
|
NPEOC-DAC |
Myelosuppression (Byun et al. 2008Byun HM, Choi SH, Laird PW, Trinh B, Siddiqui MA, Marquez VE, et al. 2'-Deoxy-N4-[2-(4-nitrophenyl) ethoxycarbonyl]-5-azacytidine: a novel inhibitor of DNA methyltransferase that requires activation by human carboxylesterase 1. Cancer Letters. 2008; 266(2): 238-248.) |
|
Mithramycin |
Malaise, Gastrointestinal effects, fever, central nervous system effects, stomatitis, epistaxis, 'ecchymoses, hemorrhage (Kennedy, 1970Kennedy B J. Metabolic and toxic effects of mithramycin during tumor therapy. Am J Med. 1970; 49(4): 494-503.) |
|
ECEG |
Anxiolytic activity, hypoglycemic activity, hypochromic anaemia, hepatotoxic effects (Mereles et al. 2011Mereles D and Hunstein W. (2011). Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises? Int J Mol Sci. 2011; 12(9), 5592-5603.) |
| HDAC inhibitors |
Valproic acid |
Neurological toxicity (Pilatrino et al. 2005Pilatrino C, Cilloni D, Messa E, Morotti A, Giugliano E, Pautasso M, et al. Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer. 2005; 104(1): 101-109.) |
|
Sodium phenylbutyrate |
Neurological toxicity only at high doses (Gore et al. 2002Gore SD, Weng LJ, Figg WD, Zhai S, Donehower RC, Dover G, et al. (2002). Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia. Clin Cancer Res. 2002; 8(4): 963-970.) |
|
AN-9 (butyric acid prodrug) |
Monotherapy was well tolerated, whereas a combination treatment with docetaxel resulted in severe toxicity and interruption of the study (Patnaik et al. 2002Patnaik A, Rowinsky EK, Villalona MA, Hammond LA, Britten CD, Siu LL, et al. A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies. Clin Cancer Res, 2002; 8(7): 2142-2148.) |
|
Suberoylanilide hydroxamic acid (hydroxamic acid derivative) |
Mild toxicity, dehydration, fatigue, diarrhoea and anorexia; thrombocytopaenia and anaemia were the doselimiting toxicities (Kelly et al. 2003Kelly WK, Richon VM, O'Connor O, Curley T, MacGregor-Curtelli B, Tong W, et al. (2003). Phase I clinical trial of histone deacetylase inhibitor suberoylanilide hydroxamic acid administered intravenously. Clin Cancer Res. 2003; 9(10):3578-3588.) |
|
FK-228 (cyclic depsipeptide) |
Bone marrow toxicity, reversible cardiac arrhythmia (which seems not to be clinically relevant), fatigue, nausea and vomiting (Piekerz et al. 2001Piekarz RL, Robey R, Sandor V, Bakke S, Wilson WH, Dahmoush L, et al. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood. 2001; 98(9):2865-2868.) |
|
MS-275 (benzamide) |
Gastrointestinal toxicities were the dose-limiting toxicities; cumulative bone marrow toxicity was also seen (Ryan et al. 2005Ryan QC, Headlee D, Acharya M, Sparreboom A, Trepel JB, Ye J, et al. (2005). Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol. 2005; 23(17): 3912-3922.) |
