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Table 1 Epigenetic clinical trials with well-known epidrugs to overcome cancer radioresistance

From: Epigenetic mechanisms underlying prostate 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

  1. 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