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Celebrex May Slow, Prevent Skin Cancers

Study Shows High-Risk Patients Had Fewer Basal Cell Cancers After Taking Celebrex

By Salynn Boyles
WebMD Health News

Reviewed By Louise Chang, MD

Jan. 5, 2009 -- There is mounting evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) may help prevent or slow the growth of non-melanoma skin cancers.

In a study published today, the Cox-2 arthritis drug Celebrex was found to reduce the growth of basal cell skin cancers by 50% in some patients with a rare genetic condition that makes them highly susceptible to the tumors.

And in a separate study reported last May, people who took Celebrex daily for nine months had 60% fewer non-melanoma skin cancers than people who did not take the drug.

Celebrex and other Cox-2 inhibitors act on the cyclooxygenase-2 enzyme involved in inflammation.

Stanford University assistant professor of dermatology Jean Y. Tang, MD, PhD, says the findings suggest a role for the cyclooxygenase enzyme in the development of basal cell carcinoma and possibly other non-melanoma skin cancers.

"Basal cell carcinomas are the most common cancer in the United States," she says. "Even though these tumors are not lethal they can have a big impact on quality of life, and we have no way to treat them short of surgical removal."

Study Ended Early Amid Vioxx Concerns

Even if Celebrex does slow skin cancer growth, it is probably not an appropriate preventive treatment for most people, Tang says.

"We certainly aren't recommending that people take this drug to reduce their risk for basal cell carcinomas," she says.

That is because of concerns about an increase in heart attack and stroke risk associated with the use of Cox-2 drugs. The Cox-2 drug Vioxx was withdrawn from the market by its manufacturer, Merck, in 2004 after studies linked its long-term use to an increase in deaths due to heart attack, stroke, and other cardiovascular events.

The study conducted by Tang, along with Ervin H. Epstein, Jr. of the Children's Hospital Oakland, was begun in 2001, before the cardiovascular risks were publicly reported.

The study included 60 patients with a very rare genetic condition known as Gorlin syndrome. Gorlin's patients can develop hundreds and even thousands of basal cell carcinomas over the course of their lives.

The study participants were treated with a standard therapeutic dose of Celebrex (200 milligrams, twice a day) or a placebo. Neither the patients nor the investigators knew which treatment was being given.

The treatment arm of the trial was stopped in 2004 in response to concerns raised by the Vioxx studies. Nevertheless, most patients received two years of active treatment and were followed for an additional year.

While both treatment groups continued to develop new cancers during the study, treatment with Celebrex was associated with a 50% decrease in the growth of skin tumors among patients who entered the trial with 15 or fewer skin tumors.

Treatment with the NSAID was also found to reduce the total number of tumors in these patients, but not in patients with more than 15 basal cell carcinoma-related skin lesions at study entry.

The findings appear in the January issue of the journal Cancer Prevention Research.

New Strategy: The Hedgehog Pathway

Tang says it remains to be seen if other oral or even topical NSAIDs can prevent or slow the growth of basal cell carcinomas and other non-melanoma skin cancers.

In an editorial published with the study, Johns Hopkins University oncologist Charles M. Rudin, MD, PhD, writes about another promising skin cancer prevention strategy, which targets something known as the hedgehog pathway.

"The hedgehog pathway is essentially a cell program that is turned on in fetal development but is normally shut off in adult tissue," Rudin tells WebMD. "But in some cancers this pathway is turned on, and basal cell carcinoma is one of those cancers."

In early studies, Rudin and colleagues showed significant reductions in skin lesions when patients with basal cell carcinomas took drugs designed to inhibit, or shut off, the hedgehog pathway.

A trial is now under way in patients with Gorlin syndrome to determine if hedgehog-inhibiting drugs prevent or slow the growth of tumors in this high-risk group.

SOURCES: Tang, J.Y. Cancer Prevention Research, January 2010; vol 3: pp 25-34.

Jean Y. Tang, MD, PhD, assistant professor of dermatology, Stanford University; The Children's Hospital Oakland Research Institute, Oakland, Calif.

Charles M. Rudin, MD, PhD, department of oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

News release, Stanford Medicine News.

Society for Investigative Dermatology, May 12, 2009.

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