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