title: Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  To discuss vorinostat approval for treatment of cutaneous manifestations of advanced cutaneous T-cell lymphoma (CTCL).
  
  
  METHODS
  Data from 1 single-arm, open-label, multicenter pivotal trial and 11 other trials submitted to support the new drug application for vorinostat in the treatment of advanced primary CTCL were reviewed. The pivotal trial assessed responses by changes in overall skin disease score using a severity-weighted assessment tool (SWAT). Vorinostat could be considered active in CTCL if observed response rate was at least 20% and the lower bound of the corresponding 95% confidence interval (95% CI) excluded 5%. Patients reported pruritus relief using a questionnaire and a visual analogue scale.
  
  
  RESULTS
  The pivotal trial enrolled 74 patients with stage IB or higher CTCL. Median number of prior treatments was 3, and 61 patients (82%) had stage IIB or higher disease. The objective response rate in the skin disease assessed by change in the overall SWAT score from the baseline was 30% (95% CI, 18.5 to 42.6) in patients with stage IIB or higher disease. Median response duration (end of response defined by 50% increase in SWAT score from the nadir) was 168 days. Median time to tumor progression was 148 days for overall population and 169 days for patients with stage IIB or higher disease. Assessment of pruritus relief was considered unreliable.
  
  
  CONCLUSIONS
  Vorinostat showed activity in CTCL, and skin responses were a clinical benefit. Vorinostat was approved for treatment of cutaneous manifestations of CTCL. A nonblinded, single-arm trial did not allow a reliable assessment of pruritus relief.
authors: Food and Drug Administration, Silver Spring, Maryland 20993, USA. bhupinder.mann@fda.hhs.gov
authors: Bhupinder S
authors: BS
authors: Mann
authors: John R
authors: JR
authors: Johnson
authors: Kun
authors: K
authors: He
authors: Rajeshwari
authors: R
authors: Sridhara
authors: Sophia
authors: S
authors: Abraham
authors: Brian P
authors: BP
authors: Booth
authors: Leigh
authors: L
authors: Verbois
authors: David E
authors: DE
authors: Morse
authors: Josephine M
authors: JM
authors: Jee
authors: Sarah
authors: S
authors: Pope
authors: Ravi S
authors: RS
authors: Harapanhalli
authors: Ramzi
authors: R
authors: Dagher
authors: Ann
authors: A
authors: Farrell
authors: Robert
authors: R
authors: Justice
authors: Richard
authors: R
authors: Pazdur
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002415:Cats; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004285:Dogs; D006801:Humans; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D018579:Patient Selection; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014481:United States; D014486:United States Food and Drug Administration; D000077337:Vorinostat
chemical_list: D016588:Anticarcinogenic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat