NCI Is Sponsoring Chemoprevention Trials of COX-2 Inhibitor

BETHESDA, Md—The National Cancer Institute (NCI), in collaboration with Searle (Skokie, Illinois, now a part of Pharmacia Corp, Peapack, New Jersey) and Pfizer Inc. (New York), is sponsoring a series of clinical trials testing celecoxib (Celebrex) for the prevention of a variety of cancerous and precancerous conditions.

Celecoxib inhibits the enzyme cyclo-oxygenase-2 (COX-2), which is induced in inflammation and precancerous tissues. The drug is currently FDA approved for the treatment of osteoarthritis and adult rheumatoid arthritis, and as an adjunct to usual care for patients with familial adenomatous polyposis (FAP).

People with FAP develop hundreds to thousands of polyps throughout their colon and rectum, beginning in adolescence. Left untreated, nearly all FAP patients develop colorectal cancer by the time they reach their 40s or 50s.

The new NCI-sponsored trials of celecoxib include the following:

• A prevention trial led by Frank Sinicrope, MD, of the M.D. Anderson Cancer Center, will test celecoxib in combination with another chemopreventive agent against FAP.

• A multicenter, randomized, placebo-controlled phase III trial headed by Monica Bertagnoli, MD, of Brigham and Women’s Hospital, will investigate whether one or two doses of celecoxib reduces the recurrence of sporadic colon polyps. The study will also seek to identify biologic markers of the progression from healthy tissue to polyps to cancer.

More than 50 centers are currently enrolling patients in the United States and the United Kingdom, and other centers will begin accepting patients shortly.

• Hereditary nonpolyposis colon cancer syndrome (HNPCC) increases the risk of cancer at a number of sites, including the colon, uterus, ovaries, stomach, urinary tract, small bowel, and bile duct.

An ongoing phase I/II study of HNPCC patients is examining the effect of one or two doses of celecoxib on cellular and molecular markers in normal-appearing rectal mucosa.

Principal investigators for the project are Patrick Lynch, MD, of M.D. Anderson Cancer Center; Henry Lynch, MD, of Creighton University; and Ilan Kirsch, MD, of NCI.

• Arlene Forastiere, MD, of Johns Hopkins University, leads a placebo-controlled phase II trial of celecoxib in patients with Barrett’s esophagus, a condition in which cells that normally line the esophagus are replaced by ones that resemble the lining of the stomach. Such patients have an increased risk of esophageal cancer.

The trial seeks to determine whether treatment causes regression of the precancerous tissue. Enrollment is underway at Johns Hopkins and will open soon at three other academic institutions.

• Bladder dysplasia, which often turns cancerous, is the subject of a phase II/III trial. Anita Sabichi, MD, of M.D. Anderson, leads the study, which tests celecoxib against placebo in patients with superficial bladder dysplasia or bladder cancer who have a high risk of recurrence. The study will assess the subsequent incidence of bladder dysplasia or cancer.

• Finally, a placebo-controlled, phase II/III study of actinic keratoses, a disorder that can lead to squamous cell skin cancer, will open at five centers later this year. Craig Elmets, MD, of the University of Alabama at Birmingham, will lead the trial.