New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer

Cang, Shundong; Ma, Yuehua; Liu, Delong

doi:10.1186/1756-8722-2-22

Journal of Hematology & Oncology

Table 3 New HDAC inhibitors in clinical trials

From: New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer

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

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ISSN: 1756-8722

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