A widely used arthritis drug reduces the incidence of non-melanoma skin cancers -- the most common cancers in humans -- according to a study published this week in the Journal of the National Cancer Institute. The COX-2 inhibitor celecoxib (brand name Celebrex), which is currently approved for the treatment of osteoarthritis, rheumatoid arthritis and acute pain in adults, led to a 62 percent reduction in non-melanoma skin cancers, which includes basal cell carcinomas and squamous cell carcinomas.
Celecoxib, a prescription-strength nonsteroidal anti-inflammatory drug (NSAID), reduced basal cell carcinomas by 68 percent and squamous cell carcinomas by 58 percent in patients at high risk for skin cancer. The decrease in the incidence of these cancers is much greater than that achieved through the use of sunscreen, which provides only moderate protection against squamous cell and basal cell carcinomas.
"For individuals who are at very high risk of skin cancer, this may be a method to reduce the number of new tumors they develop, despite the drug's known side effects," said Alice Pentland, M.D., study author and chair of the Department of Dermatology at the University of Rochester Medical Center.
Unlike many other types of cancer in which there has been a decline, the incidence of non-melanoma skin cancers is increasing at an alarming rate and is beginning to occur more frequently in younger age groups. It is estimated that the direct cost of treatment for non-melanoma skin cancers in the United States exceeds $1.4 billion each year.
The study was a double-blind, multicenter, placebo-controlled trial that included 240 patients between 37 and 87 years of age. Participants were at high risk for the development of non-melanoma skin cancers and had between 10 and 40 actinic keratoses -- rough, scaly patches about the size of the smallest fingernail that are usually found on sun-exposed areas like the arms, backs of the hands, nose and back of the neck. These come about from too much time in the sun and are prone to progress to skin cancer.
Half of the study participants received a 200 mg capsule of celecoxib twice daily and the other half were given placebo. Patients were evaluated at three, six and nine months, at which point treatment was completed, and again at 11 months, for the presence of new actinic keratoses, basal cell carcinomas and squamous cell carcinomas. Patients receiving celecoxib saw marked reductions in both cancers.
While COX-2 inhibitors such as celecoxib have beneficial effects, they are also associated with increased risk for cardiovascular and gastrointestinal side effects. In this trial researchers found no significant difference in the incidence of gastrointestinal disease, such as gastrointestinal hemorrhage or ulceration, in the two groups, nor did they observe a significant increase in cardiovascular adverse events, such as chest pain or heart attack, in patients who took celecoxib. The most commonly reported side effects included gastrointestinal disorders (12 percent) and infections (13 percent).
Study participants took celecoxib for nine months, but increases in serious cardiovascular adverse events associated with the use of some COX-2 inhibitors do not typically occur until patients have taken the medication for a year or more.
Authors believe there are several possible mechanisms by which COX-2 inhibitors such as celecoxib might slow or stop the progression of pre-cancerous cells to full-fledged tumors. COX-2 inhibitors may have an effect on the ability of non-melanoma skin cancers to grow and thrive. They may also suppress or weaken the cancer's ability to invade surrounding tissue and spread from the initial site to other parts of the body. Finally, this class of drugs may have an anti-inflammatory effect on skin cancer development.
Because the regular application of sunscreen provides only moderate protection against squamous cell and basal cell carcinomas, there has been a determined effort to identify alternative ways to prevent sunlight-induced skin cancers. As part of this effort, Pentland and her collaborators conducted preclinical studies which indicated that the enzyme cyclooxygenase-2 (COX-2) plays an important role in sunlight-induced skin cancers. These positive preclinical results led to the initiation of the current trial in humans.
Study authors stress that the identification of COX-2 inhibitors and other therapies that may prevent the incidence of skin cancer does not mean that sunscreen and other protective measures, such as wearing protective clothing and hats and avoiding outdoor activities during peak hours of sun exposure, should not be used to reduce the likelihood of skin cancer. It is likely that in the future a combination of medications that include sunscreens as well as COX inhibitors or other protective therapies will be used on a regular basis to decrease the incidence of skin cancer.
Overall, cancer caused by sunlight accounts for about half the cancer cases diagnosed in the United States. Between 1977-1978 and 1998-1999 in the Southwestern United States, the incidence of basal cell and squamous cell carcinoma increased by 50 percent and 90 percent respectively in men, and by 22 percent and 110 percent respectively in women. Similar results have been observed in the northern United States.
In addition to the University of Rochester Medical Center, the University of Alabama at Birmingham, the Veteran Affairs Medical Center, Birmingham, the University of Wisconsin, Madison, the University of Michigan, the University of California, Irvine, the Washington University School of Medicine, and the University of Texas M.D. Anderson Cancer Center participated in the study.
The trial was a cooperative effort of the participating sites, the Division of Cancer Prevention at the National Cancer Institute and Pfizer, the maker of Celebrex (brand name for celecoxib). The study was jointly funded by Pfizer and the National Cancer Institute at the National Institutes of Health.
- C. A. Elmets, J. L. Viner, A. P. Pentland, W. Cantrell, H.-Y. Lin, H. Bailey, S. Kang, K. G. Linden, M. Heffernan, M. Duvic, E. Richmond, B. E. Elewski, A. Umar, W. Bell, G. B. Gordon. Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial. JNCI Journal of the National Cancer Institute, 2010; DOI: 10.1093/jnci/djq442
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