title: Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL).
abstract: The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sézary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated.
authors.affiliation: Department of Dermatology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 434, Houston, TX 77030-4409, USA. mduvic@mdanderson.org
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Rakshandra
authors.initials: R
authors.lastname: Talpur
authors.forename: Xiao
authors.initials: X
authors.lastname: Ni
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.forename: Parul
authors.initials: P
authors.lastname: Hazarika
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kelly
authors.forename: Judy H
authors.initials: JH
authors.lastname: Chiao
authors.forename: John F
authors.initials: JF
authors.lastname: Reilly
authors.forename: Justin L
authors.initials: JL
authors.lastname: Ricker
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Richon
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003681:Dehydration / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008214:Lymphocytes / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012074:Remission Induction; D016879:Salvage Therapy; D012751:Sezary Syndrome / Q000150:complications / Q000188:drug therapy; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat