Table 2.
Selected Clinical Trials of Epigenetic Therapy in Cancer
| Epigenetic Target | Agent | Phase of Study | Disease | Findings | n | Reference |
|---|---|---|---|---|---|---|
| DNMT inhibitor alone | ||||||
| DNMTs | 5-Aza-CR | II/III | MDS and AML | Complete remission in 10-17% and hematological improvement in 23-36% | 309 | 99 |
| III | MDS | Better overall survival (24.5 vs. 15 months) than conventional care | 358 | 29 | ||
| 5-Aza-CdR | II | MDS and CMML | Anti-MDS and anti-CMML activities with a safe toxicity profile. 34% of patients achieved complete response and 73% had an objective response | 95 | 100 | |
| HDACi Alone | ||||||
| HDAC | Phenylbutyrate | I | MDS and AML | Well tolerated. No patients achieved complete or partial remission, although 4 achieved hematological improvement. | 27 | 101 |
| Vorinostat (SAHA) | I | Relapsed or refractory AML, CLL, MDS, ALL, CML | Seven out 31 AML patients showed hematological improvement, including 2 complete response and 2 complete response with incomplete blood count recovery | 41 | 102 | |
| Advanced solid and hematologic malignancies | One complete response (diffuse large B-cell lymphoma), three partial responses (cutaneous T-cell lymphoma) | 73 | 103 | |||
| Combination therapy | ||||||
| DNMTs and HDAC | 5-Aza-CR and VPA | I | Advanced solid cancers | The combination is safe; 25% of the patients showed stable disease (median, 6 months) | 55 | 95 |
| 5-Aza-CR and Phenylbutyrate | I | Refractory solid tumors | The combination is safe. No clinical benefit | 27 | 97 | |
| HDAC | Vorinostat (SAHA) and Doxorubicin | I | Solid tumors | Two out of 24 partial responses (breast and prostate cancer) and 2 stable disease for more than 8 months (melanoma) | 32 | 104 |
| Vorinostat (SAHA) plus Carboplatin and Paclitaxel | II | Advanced non-small-cell lung cancer | Better response ratio (34% vs. 12.5%), progression-free survival (6 months vs. 4.1) and overall survival (13 months vs. 9.7) than placebo plus Carboplatin and Paclitaxel | 94 | 93 | |