II. Indications
- Cutaneous T Cell Lymphoma (refractory)
III. Mechanism
- Antimetabolite, Antineoplastic Agent
- Vorinostat is a synthetic, second generation Histone Deacetylase Inhibitor (HDAC Inhibitor, hydroxamic acid-type)
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Cancers may be facilitated by abnormally expressed genes in specific histone regions
- HDAC Inhibitors block histone deacetylase
- Histone deacetylase is an enzyme that catalyzes removal of acetyl groups from core histones
- Results in hyperacetylation of histones, G1 Cell Cycle arrest, and suppresses gene expression, cell differentiation
- Activity is via upregulation of cyclin-dependant kinase p21
- Also has anti-proliferative activity via hyperacetylation of non-histone Proteins
- Tumor suppressor p53
- Alpha tubulin
- Heat-shock Protein 90
- Histones are the spools around which DNA are wrapped, and which play a role in gene expression
- Vorinostat has other activity
- Induces apoptosis and facilitates cell death
- Crosses the blood brain barrier
IV. Medications
- Vorinostat Capsules: 100 mg
V. Dosing
- See other references for disease specific dosing protocols
- Adults: 400 mg orally daily
VI. Adverse Effects
- Thromboembolism
- QTc Prolongation
- Bone Marrow Suppression with Pancytopenia
VII. Safety
- Avoid in Pregnancy (any trimester)
- Use reliable Contraception
- Avoid in Lactation
- Monitoring
VIII. Resources
Images: Related links to external sites (from Bing)
Related Studies
| Definition (NCI_NCI-GLOSS) | A drug that is used to treat cutaneous T-cell lymphoma that does not get better, gets worse, or comes back during or after treatment with other drugs. It is also being studied in the treatment of other types of cancer. Vorinostat is a type of histone deacetylase inhibitor. |
| Definition (NCI) | A synthetic hydroxamic acid derivative with antineoplastic activity. Vorinostat, a second generation polar-planar compound, binds to the catalytic domain of the histone deacetylases (HDACs). This allows the hydroxamic moiety to chelate zinc ion located in the catalytic pockets of HDAC, thereby inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors. Hyperacetylation of histone proteins results in the upregulation of the cyclin-dependant kinase p21, followed by G1 arrest. Hyperacetylation of non-histone proteins such as tumor suppressor p53, alpha tubulin, and heat-shock protein 90 produces additional anti-proliferative effects. This agent also induces apoptosis and sensitizes tumor cells to cell death processes. Vorinostat crosses the blood-brain barrier. |
| Definition (PDQ) | A synthetic agent with antineoplastic properties. Vorinostat, also known as suberoylanilide hydroxamic acid (SAHA), inhibits the enzyme histone deacetylase (HDAC), induces differentiation in some cell types, and has been shown to induce p53-independent apoptosis in a number of tumor cell lines. This agent crosses the blood-brain barrier. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37944&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37944&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1796" NCI Thesaurus) |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C111237 |
| SnomedCT | 422505001, 422523009 |
| English | N-Hydroxy-N'-phenyloctanediamide, NHNPODA, N-hydroxy-N'-phenyloctanediamide, Vorinostat, Vorinostat (substance), Vorinostat (product), Suberoylanilide Hydroxamic Acid, vorinostat (medication), suberoylanilide hydroxamic acid, vorinostat, N-Hydroxy-N'-phenyl octanediamide, vorinostat [Chemical/Ingredient], VORINOSTAT, acid hydroxamic suberoylanilide, suberanilohydroxamic acid, SAHA, Suberanilohydroxamic Acid |
| Spanish | vorinostat (producto), vorinostat, vorinostat (sustancia) |
