Originally published as JCO Early Release 10.1200/JCO.2006.10.2434 on June 18 2007

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Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma

Elise A. Olsen, Youn H. Kim, Timothy M. Kuzel, Theresa R. Pacheco, Francine M. Foss, Sareeta Parker, Stanley R. Frankel, Cong Chen, Justin L. Ricker, Jean Marie Arduino, Madeleine Duvic

From Duke University, Durham, NC; Stanford University, Stanford, CA; Northwestern University, Chicago, IL; University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO; Tufts-New England Medical Center, Boston, MA; Emory University, Atlanta, GA; Merck Research Laboratories, Upper Gwynedd, PA; and the M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Elise A. Olsen, MD, Divisions of Dermatology and Oncology, Duke University Medical Center, Durham, NC 27710; e-mail: olsen001{at}mc.duke.edu

Purpose To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes.

Patients and Methods Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated.

Results Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE.

Conclusion Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

published online ahead of print at www.jco.org on July 18, 2007.

Supported by research funding from Merck Research Laboratories.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology in Atlanta, GA, June 3-6, 2006; and at the 48th Annual Meeting of the American Society of Hematology in Orlando, FL, December 9-12, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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