Celecoxib for the prevention of sporadic colorectal adenomas.
BACKGROUND
Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia.


METHODS
We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test.


RESULTS
Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9).


CONCLUSIONS
These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).
Bertagnolli
Monica M
MM
Brigham and Women's Hospital, Boston, USA. mbertagnolli@partners.org
Eagle
Craig J
CJ
Zauber
Ann G
AG
Redston
Mark
M
Solomon
Scott D
SD
Kim
KyungMann
K
Tang
Jie
J
Rosenstein
Rebecca B
RB
Wittes
Janet
J
Corle
Donald
D
Hess
Timothy M
TM
Woloj
G Mabel
GM
Boisserie
Frédéric
F
Anderson
William F
WF
Viner
Jaye L
JL
Bagheri
Donya
D
Burn
John
J
Chung
Daniel C
DC
Dewar
Thomas
T
Foley
T Raymond
TR
Hoffman
Neville
N
Macrae
Finlay
F
Pruitt
Ronald E
RE
Saltzman
John R
JR
Salzberg
Bruce
B
Sylwestrowicz
Thomas
T
Gordon
Gary B
GB
Hawk
Ernest T
ET
D000236:Adenoma / Q000188:drug therapy / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D001241:Aspirin