Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma

Madeleine Duvic, Elise Olsen, Debra Breneman, Theresa Pacheco, Sareeta Parker, Eric Vonderheid, Rachel Abuav, Justin Ricker, Syed Rizvi, Cong Chen, Kathleen Boileau, Alexandra Gunchenko, Cesar Sanz-Rodriguez, Larisa Geskin

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Abstract

Introduction: Vorinostat, an orally active histone deacetylase inhibitor, was approved in October 2006 by the US Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease during or after treatment with 2 systemic therapies. Patients and Methods: A multicenter, open-label phase IIb trial evaluated the activity and safety of vorinostat 400 mg orally daily in patients with ≥ stage IB, persistent, progressive, or treatment-refractory mycosis fungoides or Sézary syndrome CTCL subtypes. We report the safety and tolerability of long-term vorinostat therapy in patients who experienced clinical benefit in the previous phase IIb study. Results: As of December 11, 2008, 6 of 74 patients enrolled in the original study had received vorinostat for ≥ 2 years: median age, 65 years; median number of previous therapies, 2.5; median time from diagnosis to enrollment, 1.8 years. At enrollment into the continuation phase, 5 of the 6 patients had achieved an objective response, and 1 patient had prolonged stable disease. During the follow-up study, the most common drug-related grade 1-4 adverse events (AEs) were diarrhea, nausea, fatigue, and alopecia (6, 5, 4, and 3 patients, respectively). Incidence of grade 3/4 AEs was low: anorexia (n = 1), increased creatinine phosphokinase (n = 1), pulmonary embolism (n = 1), rash (n = 1), and thrombocytopenia (n = 1). Five patients have discontinued the study drug, and 1 patient is continuing therapy. Conclusion: This post hoc subset analysis provides evidence for the long-term safety and clinical benefit of vorinostat in heavily pretreated patients with CTCL, regardless of previous treatment failures.

Original languageEnglish (US)
Pages (from-to)412-416
Number of pages5
JournalClinical Lymphoma and Myeloma
Volume9
Issue number6
DOIs
StatePublished - Dec 1 2009

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Cutaneous T-Cell Lymphoma
Safety
Therapeutics
vorinostat
Skin Manifestations
Mycosis Fungoides
Histone Deacetylase Inhibitors
Alopecia
Anorexia
United States Food and Drug Administration
Exanthema
Treatment Failure
Pulmonary Embolism
Pharmaceutical Preparations
Nausea
Fatigue
Diarrhea
Creatinine
Phosphotransferases

Keywords

  • Erythroderma
  • Histone deacetylase inhibitor
  • Mycosis fungoides
  • Sézary syndrome

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma. / Duvic, Madeleine; Olsen, Elise; Breneman, Debra; Pacheco, Theresa; Parker, Sareeta; Vonderheid, Eric; Abuav, Rachel; Ricker, Justin; Rizvi, Syed; Chen, Cong; Boileau, Kathleen; Gunchenko, Alexandra; Sanz-Rodriguez, Cesar; Geskin, Larisa.

In: Clinical Lymphoma and Myeloma, Vol. 9, No. 6, 01.12.2009, p. 412-416.

Research output: Contribution to journalArticle

Duvic, M, Olsen, E, Breneman, D, Pacheco, T, Parker, S, Vonderheid, E, Abuav, R, Ricker, J, Rizvi, S, Chen, C, Boileau, K, Gunchenko, A, Sanz-Rodriguez, C & Geskin, L 2009, 'Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma', Clinical Lymphoma and Myeloma, vol. 9, no. 6, pp. 412-416. https://doi.org/10.3816/CLM.2009.n.082
Duvic, Madeleine ; Olsen, Elise ; Breneman, Debra ; Pacheco, Theresa ; Parker, Sareeta ; Vonderheid, Eric ; Abuav, Rachel ; Ricker, Justin ; Rizvi, Syed ; Chen, Cong ; Boileau, Kathleen ; Gunchenko, Alexandra ; Sanz-Rodriguez, Cesar ; Geskin, Larisa. / Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma. In: Clinical Lymphoma and Myeloma. 2009 ; Vol. 9, No. 6. pp. 412-416.
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AU - Parker, Sareeta

AU - Vonderheid, Eric

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AU - Ricker, Justin

AU - Rizvi, Syed

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