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Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat

Madeleine Duvic1, Jenny Vu

  • 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Biologics : Targets & Therapy
|August 27, 2009
PubMed

Insights

Vorinostat, a histone deacetylase (HDAC) inhibitor, shows promise as a novel cancer therapy. It is FDA-approved for cutaneous T-cell lymphoma (CTCL) and effective in clinical trials for various advanced cancers.

Area of Science:

  • Oncology
  • Epigenetics
  • Pharmacology

Background:

  • Epigenetic modifications, specifically histone deacetylase (HDAC) activity, are implicated in cancer development.
  • Histone deacetylase inhibitors (HDACi) represent a novel therapeutic strategy targeting these epigenetic alterations.
  • Vorinostat is the first FDA-approved HDAC inhibitor for treating advanced cutaneous T-cell lymphoma (CTCL).

Purpose of the Study:

  • To evaluate the efficacy and safety of vorinostat as a cancer therapeutic.
  • To assess vorinostat's activity in solid tumors and hematologic malignancies.
  • To determine optimal dosing and response rates in patients with refractory advanced CTCL.

Main Methods:

  • Phase I, II, and III clinical trials were conducted to assess vorinostat's safety and efficacy.
  • Oral and intravenous formulations were investigated.
  • Response rates, side effects, and combination therapies were evaluated in patients with CTCL and other malignancies.

Main Results:

  • Vorinostat demonstrated activity against solid tumors and hematologic malignancies.
  • In Phase II trials for CTCL, an oral dose of 400 mg/day showed an overall response rate of 24%-30% in refractory advanced patients.
  • Common side effects included gastro-intestinal issues, fatigue, and thrombocytopenia; serious events included thrombosis.

Conclusions:

  • Vorinostat is a safe and effective HDAC inhibitor for advanced CTCL, including large cell transformation and Sézary syndrome.
  • Vorinostat exhibits therapeutic potential in various advanced cancers.
  • Combination therapies with vorinostat, radiation, and chemotherapy show synergistic or additive effects in preclinical and clinical settings.
Keywords:
Sézary syndrome (SS)Zolinza™cutaneous T-cell lymphoma (CTCL)histone deacetylase inhibitors (HDAC inhibitors)mycosis fungoides (MF)suberoylanilide hydroxamic acid (SAHA)vorinostat

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