TY - JOUR
T1 - Chemoprevention of nonmelanoma skin cancer with celecoxib
T2 - A randomized, double-blind, placebo-controlled trial
AU - Elmets, Craig A.
AU - Viner, Jaye L.
AU - Pentland, Alice P.
AU - Cantrell, Wendy
AU - Lin, Hui Yi
AU - Bailey, Howard
AU - Kang, Sewon
AU - Linden, Kenneth G.
AU - Heffernan, Michael
AU - Duvic, Madeleine
AU - Richmond, Ellen
AU - Elewski, Boni E.
AU - Umar, Asad
AU - Bell, Walter
AU - Gordon, Gary B.
N1 - Funding Information:
J. L. Viner is now employed by MedImmune, Inc. A. P. Pentland receives research grant support jointly from National Institutes of Health and corporations marketing Celebrex (celecoxib). G. B. Gordon owns stock in Pfizer, the manufacturer of Celebrex. Pfizer, Inc, had no role in the collection, analysis, or interpretation of the data, nor did Pfizer have any participation in the preparation, review, or approval of the manuscript. The National Cancer Institute contributed to the development of the protocol (Drs Viner and Hawk) and to the review of the manuscript (Drs Viner, Umar, and Ms. Richmond).
Funding Information:
The study was funded by National Cancer Institute (NCI) (N01-CN-85183 to C.A.E.); Pfizer, Inc, also partially funded this study through a clinical trials agreement with the Division of Cancer Prevention of the National Cancer Institute; the National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30 AR050948 to C.A.E.); NCI (P30 CA013148) (Edward Partridge, UAB Comprehensive Cancer Center Director); and by the Veterans Administration (C.A.E.).
PY - 2010/12/15
Y1 - 2010/12/15
N2 - BackgroundPreclinical 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 χ2 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. Conclusion sCelecoxib 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.
AB - BackgroundPreclinical 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 χ2 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. Conclusion sCelecoxib 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.
UR - http://www.scopus.com/inward/record.url?scp=78650315025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650315025&partnerID=8YFLogxK
U2 - 10.1093/jnci/djq442
DO - 10.1093/jnci/djq442
M3 - Article
C2 - 21115882
AN - SCOPUS:78650315025
SN - 0027-8874
VL - 102
SP - 1835
EP - 1844
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 24
ER -