PMID- 17962618
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20220409
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 12
IP  - 10
DP  - 2007 Oct
TI  - FDA approval summary: vorinostat for treatment of advanced primary cutaneous 
      T-cell lymphoma.
PG  - 1247-52
AB  - On October 6, 2006, the U.S. Food and Drug Administration granted regular 
      approval to vorinostat (Zolinza(R); Merck & Co., Inc., Whitehouse Station, NJ), a 
      histone deacetylase inhibitor, for the treatment of cutaneous manifestations of 
      cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or 
      recurrent disease on or following two systemic therapies. The pivotal study 
      supporting approval was a single-arm open-label phase II trial that enrolled 74 
      patients with stage IB and higher CTCL who had failed two systemic therapies (one 
      of which must have contained bexarotene). Patients received vorinostat at a dose 
      of 400 mg orally once daily, which could be reduced for toxicity to 300 mg daily 
      or 300 mg 5 days a week. The median age of patients was 61 years. Sixty-one 
      patients (82%) had stage IIB or higher CTCL and 30 patients (41%) had Sezary 
      syndrome. The median duration of protocol treatment was 118 days. The primary 
      efficacy endpoint was objective response assessed by the Severity-Weighted 
      Assessment Tool. The objective response rate was 30% (95% confidence interval 
      [CI], 19.7%-41.5%), the estimated median response duration was 168 days, and the 
      median time to tumor progression was 202 days. An additional single-center study 
      enrolled 33 patients with similar baseline and demographic features as the 
      pivotal trial. Thirteen of the 33 received vorinostat (400 mg/day). The response 
      rate in these 13 patients was 31% (95% CI, 9.1%-61.4%). The most common clinical 
      adverse events (AEs) of any grade were diarrhea (52%), fatigue (52%), nausea 
      (41%), and anorexia (24%). Grade 3 or 4 clinical AEs included fatigue (4%) and 
      pulmonary embolism (5%). Hematologic laboratory abnormalities included 
      thrombocytopenia (26%) and anemia (14%). Chemistry laboratory abnormalities 
      included increased creatinine (16%), increased serum glucose (69%), and 
      proteinuria (51%). Most abnormalities were National Cancer Institute Common 
      Terminology Criteria for Adverse Events grade 1 or 2. Grade 3 or greater 
      chemistry abnormalities included hyperglycemia, hypertriglyceridemia, and 
      hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, hyperkalemia, 
      hypercholesterolemia, hypophosphatemia, and increased creatinine.
FAU - Mann, Bhupinder S
AU  - Mann BS
AD  - Division of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. 
      Food and Drug Administration, Rockville, Maryland, USA. 
      bhupinder.mann@fda.hhs.gov
FAU - Johnson, John R
AU  - Johnson JR
FAU - Cohen, Martin H
AU  - Cohen MH
FAU - Justice, Robert
AU  - Justice R
FAU - Pazdur, Richard
AU  - Pazdur R
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 58IFB293JI (Vorinostat)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Approval
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Follow-Up Studies
MH  - Histone Deacetylase Inhibitors
MH  - Humans
MH  - Hydroxamic Acids/*therapeutic use
MH  - Lymphoma, T-Cell, Cutaneous/*drug therapy/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Salvage Therapy
MH  - Skin Neoplasms/*drug therapy/pathology
MH  - Survival Rate
MH  - Treatment Outcome
MH  - United States
MH  - United States Food and Drug Administration
MH  - Vorinostat
EDAT- 2007/10/27 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/10/27 09:00
PHST- 2007/10/27 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/10/27 09:00 [entrez]
AID - 12/10/1247 [pii]
AID - 10.1634/theoncologist.12-10-1247 [doi]
PST - ppublish
SO  - Oncologist. 2007 Oct;12(10):1247-52. doi: 10.1634/theoncologist.12-10-1247.