COLUMBUS, Ohio – One of the most popular ways to treat skin cancer could be made much more effective simply by adding celecoxib, a member of a growing class of pain relievers known as non-steroidal anti-inflammatory drugs, or NSAIDS.
Tatiana M. Oberyszyn, Ph.D.
Researchers in the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) say the addition of celecoxib to the topical chemotherapeutic agent 5-flourouracil (5-FU) is 70 percent more effective than 5-FU alone in reducing the number of tumors that developed in mice exposed to too much ultraviolet light.
The findings are currently published online and will be available in the June issue of the Journal of Investigative Dermatology.
Dr. Tatiana Oberyszyn, a member of the OSUCCC-James and senior author of the study, says early skin lesions that can lead to squamous cell carcinoma (SCC) are caused by too much exposure to the sun. Squamous cell carcinoma is one of the most common forms of skin cancer, and along with basal cell carcinoma, accounts for almost a million new cases of skin cancer every year in the United States.
“These early lesions often look like a patch of red, dry, scaly skin,” says Oberyszyn. “A lot of people think they just need to apply lotion to them and they will go away. But if it is the kind of sun damage that can develop into SCC, the patches won’t heal.”
Oberyszyn says physicians can’t tell which lesions will go on to become cancerous, so they routinely prescribe 5-FU to treat all of them. The drug can be difficult to take, however, often causing dramatic side effects like pain, inflammation, scaliness and scarring – to the point where patients choose to use it intermittently, or not at all.
“We also know that while 5-FU can be effective, it is not a sure-fire cure, and people who use it often see their tumors grow back,” says Oberyszyn. “So anything that may increase its efficacy may be useful.”
Oberyszyn and her colleagues exposed mice to ultraviolet light three times weekly for four months. At that point, all of the mice had developed at least one tumor. The researchers then randomly divided the mice into five treatment groups. The mice received either celecoxib alone, 5-FU alone, both drugs simultaneously, both drugs separately, but at different times of the day, or a placebo daily for three weeks. Following treatment, scientists measured the number and size of the tumors and observed the mice for redness or inflammation at the treatment site.
They discovered that by the third week, animals getting the combination treatment had, on average, seven fewer tumors than those receiving 5-FU alone. While not as effective as the combined treatment, treatment with both drugs given at different times of the day also reduced tumor burden. Neither 5-FU nor celecoxib alone appeared effective.
“We also found that once we stopped all treatment, the mice in all the groups experienced about the same amount of tumor regrowth, suggesting that once you start with the treatment, you need to keep going with it,” says Oberyszyn.
She says she was also disappointed to discover that the celecoxib did not appear to ease the redness and irritation caused by the 5-FU, but added that adjusting the concentration of the drug might be needed to generate an anti-inflammatory response.
The study is only in mice, but Oberyszyn says the study demonstrates proof of principle, and suggests that the approach might be appropriate to study in humans.
Additional researchers who worked on the study include Traci Wilgus at Loyola University and Thomas Breza, Jr. and Kathleen Tober at Ohio State.
The National Cancer Institute and a Ladies Auxiliary VFW Cancer Research Fellowship supported the project.
The Ohio State University Comprehensive Cancer Center is a network of interdisciplinary research programs with over 200 investigators in 13 colleges across the OSU campus, the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Children’s Hospital, in Columbus. OSUCCC members conduct research on the prevention, detection, diagnosis and treatment of cancer, generating over $75 million annually in external funding.# # #
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