Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Preclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs).


METHODS
A double-blind placebo-controlled randomized trial involving 240 subjects aged 37-87 years with 10-40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ(2) or Fisher exact tests. All statistical tests were two-sided.


RESULTS
There was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma skin cancer history, and patient time on study, the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm (RR = 0.41, 95% CI = 0.23 to 0.72, P = .002) as were the numbers of BCCs (RR = 0.40, 95% CI = 0.18 to 0.93, P = .032) and SCCs (RR = 0.42, 95% CI = 0.19 to 0.93, P = .032). Serious and cardiovascular adverse events were similar in the two groups.


CONCLUSIONS
Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers.
Department of Dermatology, 1530 3rd Ave South, EFH 414, University of Alabama at Birmingham, Birmingham, AL 35294, USA. celmets@uab.edu
Craig A
CA
Elmets
Jaye L
JL
Viner
Alice P
AP
Pentland
Wendy
W
Cantrell
Hui-Yi
HY
Lin
Howard
H
Bailey
Sewon
S
Kang
Kenneth G
KG
Linden
Michael
M
Heffernan
Madeleine
M
Duvic
Ellen
E
Richmond
Boni E
BE
Elewski
Asad
A
Umar
Walter
W
Bell
Gary B
GB
Gordon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000517:prevention & control*; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control*; D000068579:Celecoxib; D002471:Cell Transformation, Neoplastic; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib