Table 3.
New HDAC inhibitors in clinical trials
HDACI | Other agents | Dose & schedule | disease | Phase | Pts No | Outcome | Reference |
CI-994 | capecitabine | 4–6 mg/m2 | solid tumors | I | 54 | MTD:6 mg/m2 | [49,50] |
CI-994 | gemcitabine | 2–8 mg/m2 po qd | solid tumors | I | 20 | MTD:6 mg/m2+ Gem1000 mg/m2 |
[47] |
CI-994 | paclitaxel carboplatin | 4–6 mg/m2 | solid tumors | I | 30 | MTD: 4 mg/m2 | [48] |
CI-994 | 8 mg/m2 po qd | solid tumors | I/II | 53 | MTD:8 mg/m2 | [46] | |
FK228 | gemcitabine | 7–12 mg/m2 | Pancreatic, Solid tumors | I | 33 | MTD: 12 mg/m2+ Gem 800 mg/m2 |
[53] |
FK228 | 1–9 mg/m2 | thyroid, Solid tumors | I | 26 | MTD: 9 mg/m2 | [54] | |
FK228 | 18 mg/m2i.v. d1 & d5, q3w | MDS, AML | II | 12 | CR: 8% SD: 50% |
[55] | |
FK228 | 17.8 mg/m2 d1 & d7, q 3w | lung cancer | II | 19 | No response | [56] | |
FK228 | 14 mg/m2 i.v.d1, 8, 15 q4w | T-cell lymphoma | II | 42 | no myocardial damage |
[58] | |
FK228 | 13 mg/m2 i.v.d 1, 8, 15, q4w | Kidney CA | II | 29 | Insufficient activity (7% RR) |
[57] | |
ITF2357 | 150 mg or 100 mgQ12 h 4 d | MM | II | 16 | PR: 6% SD: 31% | [61] | |
ITF2357 | 100 mg PO | Hodgkins | II | 15 | SD: 54% | [60] | |
LBH589 | Docetaxel prednisone |
15–20 mg po qod | CRPC | I | 16 | Oral study closed. IV form ongoing |
[64] |
LBH589 | 20 mg day 1, 3 5 | CTCL | II | 40 | RR: 12% | [65] | |
LBH589 | 4.8–11.5 mg/m2 IV | Hematological neoplasms | I | 15 | Study halted due to QTc prolongation |
[63] | |
MGCD0103 | gemcitabine | Phase I: 50–110 mg Phase II: 90 mg |
solid tumors | I/II | 29 | MTD: 90 mg | [70] |
MGCD0103 | 12.5–56 mg/m2/d | solid tumors | I | 38 | MTD: 45 mg/m2 | [68] | |
MGCD0103 | 20–80 mg/m2 | leukemia | I | 29 | MTD: 60 mg/m2 | [69] | |
MGCD0103 | 85 mg, 110 mg | NHL | II | 50 | RR: 23% | [71] | |
MGCD0103 | 85 mg, 110 mg | HL | II | 33 | RR: 38% | [72] | |
MS-275 | 4–10 mg/m2 | leukemia | I | 38 | MTD:8 mg/m2 | [75] | |
MS-275 | 4–6 mg/m2 | Solidtumors, lymphoma | I | 27 | MTD:6 mg/m2 | [76] | |
MS-275 | 3–7 mg/m2 | melanoma | II | 28 | SD: 21–29% | [77] | |
PCI-24781 | 2.0–2.4 mg/kg | solid tumors | I | 15 | MTD: pending | [49] | |
PBA | 9–45 g/d | solid tumors | I | 28 | MTD:27 g/day | [82] | |
PBA | 150–515 mg/kg/d | solid tumors | I | 24 | MTD:410 mg/kg | [81] | |
PBA | 60 mg -360 mg/kg/d | solid tumors | I | 21 | MTD:300 mg/kg | [80] | |
PBA | 5-FU | 410 mg/kg/d | colorectal cancer | I | 9 | MTD: Not reported | [83] |
PBA | azacitidine | 200 mg/kg/d | AML MDS | II | 10 | RR:50% | [84] |
PXD101 | 1000 mg/m2/d ×5 | Ovarian ca | II | 30 | SD: 60% | [88] | |
PXD101 | 600, 900, 1000 mg/m2/day | Hematological neoplasms | I | 16 | MTD: 1000 mg/m2/day | [87] | |
PXD101 | 150–1200 mg/m2/day | solid tumors | I | 46 | MTD: 1000 mg/m2/day | [86] | |
VPA | 30–120 mg kg(-1) day(-1) IV × 5 | solid tumors | I | 26 | MTD: 60 mg/kg/day | [93] | |
VPA | ATRA | serum level 50–100 mcg/ml | AML | II | 58 | RR: 5% (not active) | [90] |
VPA | ATRA | 5–10 mg/kg | AML | I | 26 | Insufficient activity | [91] |
VPA | 20 – 40 mg/kg/d × 5 | Cervical ca | I | 12 | MTD: Not reported | [92] |
HDAC: histone deacetylase inhibitor; CR: complete responses; PR: partial response; SD: stable disease. MTD: maximal tolerated dose; RR: response rate