Celecoxib May Help Decrease Skin Cancers

Advertisement

Previous research has suggested that Celecoxib (Celebrex, Onsenal) can inhibit the development of squamous cell carcinoma in mice. This led researchers at Stanford’s School of Medicine to wonder if this non-steroidal anti-inflammatory drug (NSAID)would have a similar effect on the most common skin cancer, basal cell carcinoma (BCC).

Jean Tang, MD, PhD and her colleagues dovetailed studies in mice with a randomized, double-blinded clinical trial in humans. The results of their study is published in the January 5 issue of the journal Cancer Prevention Research.

The researchers began with a mouse model to test whether Cox-2 was involved in basal cell carcinoma. The mice used had a genetic mutation similar to that of people with basal cell carcinoma (BCC). These mice develop numerous basal cell cancers after exposure to ionizing radiation. Tang and her colleagues found that deleting the Cox-2 gene in these mice reduced their overall tumor burden (a measure of the number and sizes of the skin tumors) by 70%. Conversely, the overall size of the tumors doubled in mice engineered to express higher than usual amounts of Cox-2.

To see if the same effect could be achieved in the mice pharmacologically, the researchers fed the mice with regular doses of celecoxib to inhibit Cox-2 which resulted in a reduction of their tumor burden by 35%.

In 2001, Tang and fellow researchers then enrolled 60 people with basal cell nevus syndrome (Gorlin Syndrome), a genetic predisposition to BCC, in a double-blinded, randomized, three-year clinical trial. About half the patients received 200 mg celecoxib twice a day in a pill format, while the others received a placebo. All patients were monitored at three-month intervals at one of four study sites for the development of new BCCs or the growth of previously identified cancers.

In 2003, when the study was under way, data began to emerge about unacceptably high risks of heart attack and stroke in patients taking a different NSAID, rofecoxib (marketed by Merck & Co. under the trade name Vioxx). Due to concerns about long-term treatment with Cox-2 inhibitors, the study was discontinued. No patient died or suffered adverse cardiovascular events due to their participation in the trial.

Advertisement

Although drug treatment had been discontinued, the researchers continued to monitor basal cell carcinoma formation in people who had received the drug or placebo for an additional year to complete the three-year study.

Both groups continued to develop new cancers during the study. However, in participants who entered the study with fewer than 15 BCCs, the oral celecoxib decreased the growth of skin tumors by about 50 percent as compared to placebo. Celecoxib treatment also reduced the overall tumor burden in this group of patients.

The drug did not significantly affect tumor number or burden in patients who entered the study with more than 15 skin lesions — perhaps due to an overall difference in disease severity.

Tang is continuing her focus on skin cancer prevention at Stanford, looking at whether it’s possible to develop a topical formulation of the drug that can be applied directly to the skin to achieve a similar protective effect without associated cardiovascular risk.

Celecoxib is a NSAID used to treat mild to moderate pain and help relieve symptoms of arthritis such as inflammation, swelling, stiffness, and joint pain. It is also used to treat acute pain and menstrual cramps. Celecoxib is used to help reduce the number of polyps in the intestine for patients with familial adenomatous polyposis (FAP). It has also been associated with an increased risk of heart attack and stroke in some people.

Basal cell nevus syndrome (Gorlin Syndrome) is a rare genetic condition. The gene linked to the syndrome is passed down through families as an autosomal dominant trait. The approximate prevalence is reported to be 1 case per 56,000-164,000 population. The prevalence is likely to be considerably higher in individuals younger than 20 years who present with basal cell carcinomas (BCCs). Persons with this syndrome often have problems that involve the skin, nervous system, eyes, endocrine glands, and bones.

Sources
Stanford Medicine News
National Institute of Health

Advertisement