Pilot randomized phase II study of celecoxib in oral premalignant lesions.
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.
Papadimitrakopoulou
Vassiliki A
VA
Department of Thoracic/Head, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. vpapadim@mdanderson.org
William
William N
WN
Dannenberg
Andrew J
AJ
Lippman
Scott M
SM
Lee
J Jack
JJ
Ondrey
Frank G
FG
Peterson
Douglas E
DE
Feng
Lei
L
Atwell
Anthea
A
El-Naggar
Adel K
AK
Nathan
Cherie-Ann
CO
Helman
Joseph I
JI
Du
Baoheng
B
Yueh
Bevan
B
Boyle
Jay O
JO
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D010919:Placebos; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib