BETHESDA, MdThe 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 Womens
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
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
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
Barretts 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
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.