COX-2 Inhibitors

Are COX-2 Inhibitors Safe?

Dr. Banu Arun

Dr. Banu Arun, an assistant professor in the Department of Breast Medical Oncology, is studying the possible role of celecoxib in the prevention of breast cancer. To ensure patient safety, the data from all ongoing, long-term trials of COX-2 inhibitors are undergoing intensive review by the NCI.

by Dianne Witter

Cyclooxygenase-2 (COX-2) inhibitors have become a staple in the arsenal of non-steroidal anti-inflammatory drugs, considered as effective as aspirin without the gastrointestinal side effects. Recently, the COX-2 inhibitor celecoxib (Celebrex) has shown substantial promise for treatment and chemoprevention of cancer, and it is currently the focus of more than 40 National Cancer Institute (NCI) trials around the country, some at M. D. Anderson Cancer Center.

But with the recent voluntary recall of rofecoxib (Vioxx), another COX-2 inhibitor, from the market due to concerns that it may cause increased risk of cardiovascular problems, many physicians—and their patients—are wondering whether all COX-2 inhibitors might pose similar safety problems.

In response to the recall, the NCI is conducting a rapid but thorough review of data from long-term trials of COX-2 inhibitors through its Data Safety Monitoring Boards. However, scientists say that Vioxx and Celebrex differ substantially in their molecular makeup and in how long they stay in the body. They’re thought to work through different cellular pathways and therefore may be less likely to cause the same problems.

“COX-2 inhibitors differ in their degree of COX-2 specificity and inhibitory activity and probably more importantly in their interactions with non-COX-2 targets,” said Bernard Levin, vice president for cancer prevention and population sciences at M. D. Anderson and co-principal investigator of a study using celecoxib as a chemoprevention agent for colorectal polyps. “Three long-term international trials of celecoxib are undergoing careful scrutiny to assess whether there is any evidence of cardiovascular harm, and this information should be available within the next few months.”

The experience with Vioxx, however, is a valuable reminder that, no matter what the safety record, all drugs have some risks. The decision to prescribe a drug or to study a drug in a clinical trial requires carefully weighing the potential risks and benefits. This is especially important in the field of chemoprevention, in which new agents must be studied for years to determine their preventative effects.

“An agent used over many years by patients who are asymptomatic and may not have a serious disease has to meet high safety standards,” Dr. Levin said. “The best way to determine if a drug has any adverse effects is in long-term, randomized, blinded, placebo-controlled trials monitored by independent Data Safety Monitoring Boards with appropriate expertise.”

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

Other articles in OncoLog, December 2004 issue: