Editor’s note: BioWatch is a regular feature on Fridays.Doctors are likely to start prescribing Cox-2 inhibitors such as Pfizer’s Celebrex for off-label indications such as cancer prevention if studies continue to show their anti-cancer effects, says a University of North Carolina at Chapel Hill School of Medicine researcher.

Dr. Raj S. Pruthi is conducting ongoing studies of how well Cox-2 inhibitors such as celecoxib, marketed as Celebrex by Pfizer as an anti-inflammatory drug for arthritis sufferers, slow the recurrence of prostate cancer. Pruthi, assistant professor of surgery-urology at the School of Medicine, also co-directs the multidisciplinary program for urologic oncology at the UNC Lineberger Comprehensive Cancer Center.

The study suggests the drug may slow progression of the disease in men with elevated PSA levels indicating the cancer’s recurrence.

Currently, Pruthi notes, there’s no effective treatment options for the estimated 50,000 men who annually see the first signs of prostate cancer recurrence, called biochemical relapse, a detectable and rising PSA level after surgery or radiation therapy.

“The good news is that if the PSA test points to a recurrence, it gives us a lead time of up to seven years. The bad news is that we don’t have anything appropriate and effective to offer at this stage of recurrence,” he explains.

Cox-2 inhibitors may be the needed alternative, Pruthi says.

Anti-cancer effects

In the laboratory, Cox-2 inhibitors have been shown to have anti-tumor activities in human colon, breast, lung and prostate cancer tissues. “Recent evidence has shown that Cox-2 is over-expressed in human prostate cancer tissue and that Cox-2 inhibition has potent anti-tumor activity,” Pruthi tells Local Tech Wire.

During the last 15 years, evidence from epidemiologic studies has suggested that people who take non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief have a reduced risk of colon cancer. More recent studies have suggested that this reduced risk may be true for prostate cancer, as well.

These drugs, including aspirin, block Cox-2 produced in response to injury. Cox-2 enhances the inflammatory response, resulting in pain, inflammation and swelling. Ibuprofen (Advil, Motrin) blocks Cox-2 more strongly than aspirin, but also interferes with aspirin’s heart protecting blood-thinning effects.

Easier on the stomach

NSAIDs also block expression of Cox-1, produced constantly to help preserve the stomach’s lining. Hence, the increased risk of gastrointestinal side effects associated with taking NSAIDs. The Cox-2 inhibitors lack those side effects.

Pruthi says he initiated the study of inhibiting Cox-2 in prostate cancer patients in biochemical relapse because of all the data suggesting they have anti-cancer effects.

Off-label use

In an earlier clinical study, people at hereditarily high risk for developing pre-cancerous colon polyps received celecoxib. They showed a decrease in the number of these polyps. Consequently, the FDA has approved the use of celecoxib for the prevention of pre-cancerous polyps in these patients. Presently, that’s the only anti-cancer indication for these drugs, but Pruthi says doctors are likely to prescribe them off-label indications if clinical data shows they are effective anti-cancer fighters.

Pruthi’s UNC study showed a significant inhibitory effect on the PSA levels in 22 of 24 patients after three months. PSA levels actually declined or stabilized in 11 patients. Of the remaining 13, 11 more saw “a dramatic slowing their PSA doubling time.”

“As we go through the data on prostate cancer and Cox-2 inhibitors, there’s as much supporting these as anti-cancer drugs as for many others we try. Pfizer hasn’t pushed this effect. They’re just beginning to get on board. They’re making so much money off of Celebrex as an anti-inflammatory they haven’t been thinking about this. But the science behind it is good.”

But no law prevents doctors from using the drugs off-label, Pruthi says. He notes that once science supports the use of a drug for a particular indication, doctors often start using it for that indication even without U.S. Food and Drug Administration (FDA) approval. “You just can’t market it for that indication without FDA approval,” he says.

“The goal,” Pruthi says, “is to find out if Cox-2 inhibitors can be used as a preventative. It may apply to other areas of cancer, as well. The idea being that if you’re high risk, your father had prostate cancer, you turn 40 and start taking it. Ultimately, what we want to do is not just treat cancer, but prevent it.”

Up to 100 patients will be studied in this ongoing UNC investigation this summer.