Celecoxib Approved as Adjunct for Patients With Familial Adenomatous Polyposis

The Food and Drug Administration (FDA) recently approved celecoxib (Celebrex) as an oral adjunct to the standard care (eg, endoscopic surveillance and surgery) of patients with familial adenomatous polyposis (FAP). Celecoxib, the only cyclooxygenase-2 (COX-2) specific inhibitor indicated for the treatment of both osteoarthritis and adult rheumatoid arthritis, is the first pharmacologic agent to be indicated to reduce the number of adenomatous colorectal polyps in patients with FAP.

“We are committed to fulfilling unmet medical needs for people who must live day to day with this severe and life-altering disease. The National Cancer Institute’s sponsorship of the FAP clinical study underscores the importance of medical research into the needs of patient populations with devastating conditions,” said Philip Needleman, PhD, co-president, Searle, and chief scientist, Monsanto, who discovered Celebrex. “We are just beginning to unlock the potential of Celebrex beyond arthritis.”

Important Additional Treatment Option

Familial adenomatous polyposis is characterized by the development of hundreds to thousands of potentially precancerous (adenomatous) polyps in the colon and rectum. Many of these polyps express high levels of COX-2, compared to normal adjacent tissue, and may be precursor lesions for colorectal cancer. Left untreated, virtually all patients with FAP develop colorectal cancer by age 40 to 50 years, and to date, no drugs have been approved for the care of patients with FAP.

A 6-month, 83-patient clinical trial, sponsored by the National Cancer Institute’s Division of Cancer Prevention in collaboration with Searle, is the largest randomized, double-blind, placebo-controlled trial to date in FAP. The study demonstrated that an oral, 400-mg dose of celecoxib twice daily significantly reduced the number of adenomatous colorectal polyps by an average of 28%—compared to a 5% reduction with placebo. The study was conducted at the University of Texas, M. D. Anderson Cancer Center in Houston, as well as at St. Mark’s Hospital in London.

“This is the first real breakthrough in our ability to offer FAP patients a proven adjunctive therapy to usual care,” said Gideon Steinbach, MD, one of the study’s lead investigators and assistant professor of medicine, the University of Texas, M. D. Anderson Cancer Center.

“FAP is a life-threatening disease that urgently requires new treatment options in addition to what is now available. We believe that the FDA’s approval of Celebrex represents an important step forward in bringing hope and state-of-the-art care to people with FAP,” said Carolyn Aldige, president and founder, Cancer Research Foundation of America.

In the FAP trial, common side effects of celecoxib were diarrhea and dyspepsia. Celecoxib has not been shown to reduce the risk of gastrointestinal (GI) cancer or the need for any FAP-related surgeries. Therefore, usual endoscopic surveillance and surgery schedules should not be altered in patients treated with the drug.

Future Trials to Assess Drug’s Effect on Cancer Development

Since the current trial did not include a cancer end point, the effect of celecoxib on the development of cancer has not yet been established. Searle and Pfizer will be conducting further studies to assess the clinical benefit of celecoxib in this regard. Searle and Pfizer are also conducting research, in collaboration with the National Cancer Institute, into the use of celecoxib in patients with sporadic adenomatous polyps (SAP) of the colon, Barrett’s esophagus, actinic keratosis, and superficial bladder cancer.