Vorinostat, Zolinza

  • Indications
  1. Cutaneous T Cell Lymphoma (refractory)
  • Mechanism
  1. Antimetabolite, Antineoplastic Agent
  2. Vorinostat is a synthetic, second generation Histone Deacetylase Inhibitor (HDAC Inhibitor, hydroxamic acid-type)
    1. Histones are the spools around which DNA are wrapped, and which play a role in gene expression
      1. Cancers may be facilitated by abnormally expressed genes in specific histone regions
    2. HDAC Inhibitors block histone deacetylase
      1. Histone deacetylase is an enzyme that catalyzes removal of acetyl groups from core histones
      2. Results in hyperacetylation of histones, G1 cell cycle arrest, and suppresses gene expression, cell differentiation
        1. Activity is via upregulation of cyclin-dependant kinase p21
      3. Also has anti-proliferative activity via hyperacetylation of non-histone Proteins
        1. Tumor suppressor p53
        2. Alpha tubulin
        3. Heat-shock Protein 90
  3. Vorinostat has other activity
    1. Induces apoptosis and facilitates cell death
    2. Crosses the blood brain barrier
  • Medications
  1. Vorinostat Capsules: 100 mg
  • Dosing
  1. See other references for disease specific dosing protocols
  2. Adults: 400 mg orally daily
  • Safety
  1. Avoid in Pregnancy (any trimester)
    1. Use reliable Contraception
  2. Avoid in Lactation
  3. Monitoring
    1. Complete Blood Count
    2. Electrolytes
    3. Renal Function tests
    4. Electrocardiogram