A	B	C	D	E	F	G	H	I	J
1	Main
2		Brand Name	Zolinza
3		Generic Name	Vorinostat, suberoylanilide hydroxamic acid, SAHA
4		Price	$87,600/year. $60 per 100mg
5		Market	An indolent NHL with 1500 pts/year.
6
7			SAHA IV - 2 hr infusion 2-15d - DLT: thrombocytopenia, neutropenia - T1/2 = 30 min - 1 PR in Hodgkins
8			SAHA PO - qd/bid - DLT fatigue, N/V, dehydration - T1/2 ~ 2 hrs - 1 CR DLBCL, 5 PR
9
10			HDACs (histone deacetylase) pathway:
11			HDAC is a TF with a subset of genes incl. p21. Upstream is SAHA which signals chromatin condensation and open chromatin/transcription
12			blocking results in growth inhibition, apoptosis and differentation
13			(pnas, nature sources)							thymalidate synthase
14
15			SAHA in relapsed/refractory CTCL, n=33
16			3 different oral dosing schedules, 8 patients with benefit. 31% PR, 54% "evidence of benefit" at 400mg
17
18			file in 2006 for CTCL. Data at ASCO
19			confirmatory p2b study ongoing
20
21
22
23
24			histone deacetylase inhibitors
25
26
27
28			Aliphatic acids		cyclic peptides		hydroximates		benzamides
29			phenylbutyrate		depsipeptide		saha		ms-275
30			penylacetate				pyroxamide		ci-994
31			pivanex				cbha
32			valproic acid				laq824
33							lbh589a
34							pxd-101
35
36
37			other HDAC: p2 CI-994 (PFE), Pivanex (TTP), FK-228 (Gloucester), PXD-101 (CRGN/TopoTarget), LBH-589 (NVS), MS-275 (SHR), MGCD-0103 (MYG TO/PHRM)
38
39
40			CTCL 1500/year - NHL
41
42			p1 nsclc 56% PR, 22% SD in combo with carbo-tax. Also in p3 for mesothelioma, p2 for leukemia/lymphoma, breast, lung, prostate, renal, thyroid, melanoma, brain, H&N