The Efficacy of Vorinostat in Combination With Interferon Alpha and Extracorporeal Photopheresis in Late Stage Mycosis Fungoides and Sézary Syndrome
April 2011 | Volume 10 | Issue 4 | Original Article | 403 | Copyright © 2011
Hatice Sanli MD,a Bengu Nisa Akay MD,a Rana Anadolu MD,a Muhit Ozcan MD,b Secil Saral MD,a Aynur Akyol MDa
aDepartment of Dermatology, Ankara University School of Medicine, Turkey
bDepartment of Hematology, Ankara University School of Medicine, Turkey
Objective: Long-term survival for advanced stages of mycosis fungoides (MF) may be beneficially affected by the use of multimodality
therapy. We aim to evaluate the activity of vorinostat in combination with interferon (IFN) alpha and extracorporeal photopheresis
(ECP) with persistent, progressive advanced stage MF and Sezary syndrome (SS).
Patients and Methods: Three patients with stage IIB-IVA MF/SS were treated with vorinostat 400 mg/day/po. Vorinostat was added to ongoing ECP and IFN-alpha-2a therapies in all three patients.
Results: The patient with stage IIB MF achieved a complete response. The patient with SS showed a stable disease of less than 50 percent improvement in body surface area with reduction in the sizes of axillary and inguinal lymph nodes. A partial remission was maintained for 24 weeks in the patient with stage IVA MF, followed by rapid disease progression under treatment which led to cessation of vorinostat treatment due to study criteria as well as serious side effects.
Conclusion: Our experience in this case series is suggestive of the synergistic effect of vorinostat in combination with IFN and ECP and supports the efficacy of vorinostat in inducing prolonged responses in patients with progressive disease and/or stable disease in otherwise progressive and treatment refractory late stage MF/SS.
J Drugs Dermatol. 2011;10(4):403-408.
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Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of diseases with diverse clinical manifestations and prognoses. Standard treatments for early stage CTCL include topical corticosteroids, imiquimod, psoralen and ultraviolet A phototherapy (PUVA), narrow-band ultraviolet B, systemic and topical retinoids, electron beam radiation and topical chemotherapy.1,2 IFN-alpha-2a is a common therapeutic agent for MF/SS, especially in combination with PUVA.2,3 Recent studies further focused on targeted chemotherapy (denileukin diftitox, bexarotene, gemcitabine, alemtuzumab) in the treatment of advanced stage, persistent and recurrent MF/SS.4-8 ECP, as an immunostimulating intervention, has been reported to increase overall survival for advanced-stage patients.9 In October 2006, the U.S. Food and Drug Administration granted regular approval to vorinostat (Zolinza,®; Merck & Co., Inc., Whitehouse Station, NJ), for the treatment of cutaneous manifestations of CTCL in patients with progressive, persistent, or recurrent disease on or following two systemic therapies. The pivotal study supporting approval was a single-arm open-label phase II trial.10
The aim of the present case study is to evaluate the efficacy of vorinostat in combination with IFN-alpha-2a and ECP in persistent, progressive advanced stage MF/SS.
patients, materials and methods
Two patients with advanced stage MF and one patient with SS were included in this case study. Staging was performed according to the TNM staging system.11 Patients' demographic data are presented in Table 1. All patients underwent ECP using the UVAR XTS system (Therakos, Exton, PA, USA). Each cycle of ECP consisted of two daily procedures at two consecutive