Skin cancer protection in a pill
U. ROCHESTER (US) —A drug widely used to treat arthritis offers better protection from non-melanoma skin cancers than sunscreen, research shows.
The COX-2 inhibitor celecoxib (brand name Celebrex) led to a 62 percent reduction in non-melanoma skin cancers, which includes basal cell carcinomas and squamous cell carcinomas. The rate of decrease is much greater than that achieved through the use of sunscreen, which provides only moderate protection against the same cancers.
Details are reported in the Journal of the National Cancer Institute.
“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,” says Alice Pentland, study author and chair of the dermatology department at the University of Rochester.
Unlike many other types of cancer in which there has been a decline, the incidence of non-melanoma skin cancers is increasing 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, currently approved for the treatment of osteoarthritis, rheumatoid arthritis, and acute pain in adults, 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.
The study 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 nonsteroidal anti-inflammatory drugs (NSAID) 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 that indicated 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.
Researchers from the University of Alabama at Birmingham; University of Wisconsin, Madison; University of Michigan; the University of California, Irvine; Washington University School of Medicine; and the University of Texas M.D. Anderson Cancer Center participated in the study.
The study was jointly funded by Pfizer (the maker of Celebrex) and the National Cancer Institute at the National Institutes of Health.
More news from the University of Rochester: www.rochester.edu/news