Table 1.
Epigenetic therapeutics (mono- and combined) in NSCLC patients
| Epigenetic agent | Phase | Total patient # | Patient # with NSCLC | Response rate | CR/PR | SD | OS month | Side effects | Study status | NCT number | Reference | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DNMTi | ||||||||||||
|
| ||||||||||||
| decitabine | 1 | EC, LC, pleural meso (35) | 20 | - | - | - | grade 4 neutropenia (15), grade 3 leukopenia, thrombocytopenia or anemia in (20) of 35, (2) of 35, and (3) of 35 patients | completed | NCT00019825 | [4] | ||
|
| ||||||||||||
| HDACi | ||||||||||||
|
| ||||||||||||
| belinostat | 1 | - | - | - | - | - | not yet published | completed | NCT00413075 | [5] | ||
| entinostat | 1 | refractory solid tumors and lymphomas (27) | 2 | better in lower dose | 1/2 | - | frequent hypophosphatemia | completed | NCT00020579 | [6, 7] | ||
| romidepsin | 2 | 19 | 16 | no objective responses | 9 | - | grade 3 anemia (3), grade 3/4 neutropenia (4), grade 4 thrombocytopenia (1), grade 3 hypoxia (3), pneumonitis (1), tumor pain (1), thrombosis (1), cellulitis at injection site (2), pulmonary embolism (1) | completed | NCT00020202 | [8] | ||
| vorinostat | 2 | 16 | 16 | 2 progressed after 1 cycle (2), included in further analyses (14) | - | 7.1 | 9 SAE: neutropenia (3), pulmonary embolism (2), hyperglycemia (1), thrombosis (1), dyspnea (1), cerebrovascular accident (1), 16 AE: neutropenia (6), hyperglycemia (5), lymphopenia (3), fatigue (4), pneumonia (1) | completed | NCT00138203 | [9] | ||
|
| ||||||||||||
| DNMTi | HDACi | |||||||||||
|
| ||||||||||||
| azacitidine | entinostat | 1/2 | 45 | 45 | see next columns | 1/1 | 10 | therapy cycle 1: grade 3: hematologic toxicities (9), gastrointestinal symptoms (6), electrolyte disturbances (3), general symptoms (5), grade 4: hematologic toxicities (3); therapy cycle ≥2: grade 3: hematologic toxicities (9), gastro intestinal (1), endocrine (1), general symptoms (5); grade 4: hematological toxicities (3) | completed | NCT00387465 | [10] | |
| azacitidine | entinostat | - | - | Stage I NSCLC | - | - | - | not yet published | terminated | NCT01207726 | [11] | |
| azacitidine | entinostat | 1 | - | Stage I NSCLC | - | - | - | not yet published | terminated | NCT01886573 | [12] | |
| azacitidine | entinostat | - | - | - | - | - | - | not yet published | terminated | NCT01935947 | [13] | |
| decitabine | valproic acid | 1 | 8 | 8 | - | - | 1 | grade 3 neurotoxicity (2) | terminated earlier (initially 25 planned) | NCT00084981 | [14] | |
Abbreviations: AE: adverse event; CR: complete response; DNMTi: DNA methyltransferase inhibitor; EC: esophageal cancer; HDACi: histone deacetylase inhibitor; LC: lung cancer; meso: mesothelioma; NCT Number: ClinicalTrials.gov identifier; NSCLC: non-small cell lung cancer; OS: overall survival; PR: partial response; SAE: serious adverse event; SD: stable disease; (−): data not available.