- Class: Histone deacetylase (HDAC) inhibitor – epigenetic modifier.
- Type: Oral small molecule.
Mechanism of Action (MOA)
- Inhibits histone deacetylases (class I and II HDACs) → increases acetylation of histone proteins.
- Leads to relaxation of chromatin, altering gene expression:
- Promotes cell cycle arrest (G1 phase)
- Induces apoptosis
- Inhibits angiogenesis and tumor cell proliferation
Clinical Uses
- Cutaneous T-cell lymphoma (CTCL) – for patients with progressive, persistent, or recurrent disease after at least one prior systemic therapy.
- Investigational in other hematologic malignancies and solid tumors.
Dosing (Adults)
- 400 mg orally once daily, with or without food.
- Dose adjustments for:
- Hepatic impairment (Child-Pugh B/C → reduce dose)
- Severe renal impairment or toxicity
Toxicities
- Gastrointestinal: nausea, vomiting, diarrhea, anorexia.
- Hematologic: thrombocytopenia, anemia, neutropenia.
- Fatigue, insomnia.
- Electrolyte disturbances: hypocalcemia, hypokalemia, hypomagnesemia.
- QT prolongation – monitor ECG in at-risk patients.
- Rare: pulmonary toxicity (dyspnea, cough), liver enzyme elevation.
Monitoring
- CBC with differential regularly.
- Liver function tests (AST, ALT, bilirubin).
- Electrolytes (Ca, K, Mg) – supplement as needed.
- ECG for QT interval monitoring in high-risk patients.
- Monitor for GI toxicity and weight loss.
Summary
Vorinostat (Zolinza®) is an oral HDAC inhibitor for CTCL. Key concerns include hematologic toxicity, GI side effects, electrolyte disturbances, and QT prolongation, requiring regular CBC, liver function, electrolyte monitoring, and ECG if indicated.