Table 1.
Epigenetic clinical trials with well-known epidrugs to overcome cancer radioresistance
| Drug | Clinical trials | Target | Cancer type | Patients | Doses | OS rates | Year of publication | References | Study ID |
|---|---|---|---|---|---|---|---|---|---|
| SAHA | Phase I | HDACi | Brain metastasis | 4 completed study protocol | 400 mg/day with 37.5 Gy (2.5 Gy/fr.) over 5 weeks | 36 weeks | 2014 | [119] | NCT01600742 |
| SAHA | Phase I | HDACi | NSCLC brain metastasis | 12 completed study protocol | 200–400 mg/day for 14 days with SD of SRS at day 3 | 13 months | 2017 | [120] | NCT00946673 |
| SAHA | Phase I/II | HDACi | Glioblastoma | Phase I: 15 Phase II: 107 | 300 or 400 mg/day with Std TMZ + RT | 55.1%, 15 months FU | 2018 | [121] | NCT00731731 |
| SAHA | Phase I | HDACi | Advanced head and neck SCC | 26 completed study protocol | 100–400 mg, 3 × weekly with concurrent CRT | 96.2% CR at 33.8 months FU | 2019 | [122] | NCT01064921 |
| VPA | Phase II | HDACi | Glioblastoma | 37 completed study protocol | 25 mg/kg oral divided in 2 dd concurrent with RT and TMZ | 97%, 86%, and 65% at 6, 12, and 24 months FU, respectively | 2015 | [123] | NIHMS686154 |
| VPA + Hydralazine | Phase III | HDACi + DNMTi | Stage III cervical cancer | 18 completed study protocol | 182 mg or 83 mg of hydralazine and 30 mg/kg VPA plus TCD of 85 Gy | NS | 2010 | [124] | NCT02446652 |
| LBH-589 | Phase I | HDACi | Stage III NSCLC | 9 with pRT | 20, 30, 45 mg twice/week, with pRT or rCRT | 9 months | 2015 | [125] | NA |
| LBH-589 | Phase I | HDACi | High grade gliomas | 12 completed study protocol | 10, 20, 30 mg/day, with 30–35 Gy (10 fr.) | 7.8; 6.1, and 16.1 for each drug concentration, respectively | 2016 | [126] | NCT01324635 |
| LBH-589 | Phase I | HDACi | HNC, PCa and Esophageal cancer | 7 completed study protocol | NS | NS | 2017 | NP | NCT00670553 |
CR, complete response; CRT, chemoradiotherapy; DNMTi, DNA methyltransferase inhibitors; FU, follow-up; Fr., fraction; HDACi, histone deacetylase inhibitors; HNC, Head and neck cancer; NS, not specified; OS, overall survival; RT, radiotherapy; TMZ, temozolomide; VPA, Valproic acid; pRT, palliative radiotherapy; PCa, prostate cancer; NA, not available; NP, not published; NS, not specified; NSCLC, non-small cell lung cancer; SCC, squamous cell carcinoma; SD, standard dose; SRS, stereotactic radiosurgery