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 © April 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
Abstract
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.
INTRODUCTION
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
