title: Pilot randomized phase II study of celecoxib in oral premalignant lesions.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2)-specific inhibition suppresses carcinogenesis in preclinical models and is a promising strategy for preventing oral cancer. In this pilot randomized phase II study, we evaluated the efficacy and safety of the COX-2 inhibitor celecoxib in patients with oral premalignant lesions (OPL).
  
  
  METHODS
  Patients were randomly assigned to placebo (n=18), celecoxib 100 mg twice daily (n=17), or celecoxib 200 mg twice daily (n=15) for 12 weeks. Six additional patients received celecoxib (400 mg twice daily) in an unblinded extension of the study. Biopsies were obtained at baseline and week 12. All patients entering the study were required to have at least one histologically confirmed early (atypical hyperplasia, atypical hyperkeratosis, or mild dysplasia) or advanced (moderate to severe dysplasia) OPL.
  
  
  RESULTS
  Forty-nine patients (46 of 50 randomized and 3 of 6 open label) were evaluable for efficacy analyses. There were no statistically significant differences between the response rates of the randomly assigned arms: placebo, 33.3% (6 of 18); celecoxib 100 mg twice daily, 41.2% (7 of 17); and celecoxib 200 mg twice daily, 20.0% (3 of 15). Two patients responded on celecoxib 400 mg twice daily. Celecoxib was generally well tolerated. Patients with higher baseline COX-2 mRNA levels had an increased risk of disease progression within 3 months.
  
  
  CONCLUSIONS
  Celecoxib at 100 or 200 mg twice daily was ineffective in controlling OPLs in this randomized controlled trial. This result and cardiovascular toxicity results of other (large scale) randomized controlled trials of selective COX-2 inhibitors have discouraged the continued investigation of these agents in oral cancer chemoprevention. Better methods for identifying high-risk patients and more active interventions are needed for future oral cancer chemoprevention trials.
authors.affiliation: Department of Thoracic/Head, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. vpapadim@mdanderson.org
authors.forename: Vassiliki A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Peterson
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Anthea
authors.initials: A
authors.lastname: Atwell
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Cherie-Ann
authors.initials: CO
authors.lastname: Nathan
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Helman
authors.forename: Baoheng
authors.initials: B
authors.lastname: Du
authors.forename: Bevan
authors.initials: B
authors.lastname: Yueh
authors.forename: Jay O
authors.initials: JO
authors.lastname: Boyle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D010865:Pilot Projects; D010919:Placebos; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D010919:Placebos; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib