Vorinostat (suberoylanilide hydroxamic acid, SAHA) is clinically active in advanced cutaneous T-cell lymphoma (CTCL): Results of a phase IIb trial

Abstract

7500 Background: Vorinostat is a histone deacetylase inhibitor that has demonstrated clinical activity at tolerable dose levels in patients (pts) with advanced CTCL in phase I and IIa trials. Methods: Open-label, single-arm, nonrandomized phase IIb trial of oral vorinostat 400 mg daily until disease progression or intolerable toxicity. Eligibility: advanced CTCL; ≥ 2 prior systemic therapies which must have included bexarotene unless unable to tolerate; adequate hematologic, hepatic and renal function. Planned sample size: ≥ 50 evaluable pts with clinical stage ≥ IIB. Primary endpoint: objective response rate (OR = CR + PR) as measured by a modified skin severity weighted assessment tool. The study would be positive if OR in ≥ stage IIB pts was ≥ 20%. Secondary endpoints: assessment of response duration (DOR), time to progression (TTP), time to response (TTR), pruritus relief and safety. Results: Seventy-four pts (median age, 60 y [range, 39–83]; median 3 prior systemic therapies) were enrolled (61 pts ≥ stage IIB) from 9/04 to 5/05 at 18 centers. Data cut-off was 11/05 with a median follow-up of 4 months. Efficacy data are shown in Table 1 . The OR was 29.5% (18 PR including 1 with later CR) in ≥ stage IIB pts. Median TTP was 148 d for all pts and 203.5+ d for responders. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%) and anorexia (26%), and were mostly ≤ Grade 2. Drug-related ECG changes were Grade 1 in 5 pts (7%) and Grade 2 in 1 pt (1%), but not associated with cardiac symptoms. Seven pts discontinued and 10 had dose modification due to drug-related AE. Drug-related AE ≥ Grade 3 included fatigue (5%), pulmonary embolism (5%), nausea (4%) and thrombocytopenia (4%). Twenty-five pts discontinued due to progressive disease. Causes of the 3 deaths on study were: unknown (d 2), ischemic stroke (d 227) and disease progression (d 52). Conclusion: Oral vorinostat is effective in the treatment of advanced CTCL with an acceptable safety profile. [Table: see text] [Table: see text]