title: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  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.
  
  
  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 ( > or = 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 >or = 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.
  
  
  CONCLUSIONS
  Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.
authors.affiliation: Duke University, Durham, NC, USA. olsen001@mc.duke.edu
authors.forename: Elise A
authors.initials: EA
authors.lastname: Olsen
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Pacheco
authors.forename: Francine M
authors.initials: FM
authors.lastname: Foss
authors.forename: Sareeta
authors.initials: S
authors.lastname: Parker
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Justin L
authors.initials: JL
authors.lastname: Ricker
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Arduino
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat