Vorinostat

• 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.