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A proposed new use for a prescription arthritis drug may help patients with a
rare, genetic disease that almost inevitably leads to colorectal cancer.
The U.S. Food and Drug Administration has approved the use of
celecoxib (Celebrex TM, made by Searle Monsanto) for the reduction and regression of adenomatous
colorectal polyps in patients with familial adenomatous polyposis or FAP.
People with FAP develop hundreds to thousands of polyps throughout their colon
and rectum, beginning in adolescence. Left untreated, nearly all patients
develop colorectal cancer by their 40s and 50s. The primary treatment of the
disease is surgical removal of most or all of the colon and rectum. It is
estimated that about one in 10,000 people have this disease.
In an NCI-sponsored, Phase II, randomized controlled clinical trial, 83
patients with FAP received either a placebo, 100 mg of celecoxib twice daily,
or 400 mg of celecoxib twice daily for six months. Measurements of the number
and size of polyps in a marked area of the colon and rectum were made and
videotapes of the colorectum were also reviewed by five reviewers blinded to
patient treatment assignments. Patients receiving the 400 mg dose of celecoxib
had an average of 28 percent fewer new polyps at the end of the study, and 23
of 30 of the patients had a decrease in the number of existing polyps.
Patients receiving the placebo had 4.5 percent fewer polyps at the end of the
trial and those taking the 100 mg dose had 14.5 percent fewer polyps.
Celecoxib is similar to nonsteroidal anti-inflammatories (NSAIDs) such as
aspirin or ibuprofen. NSAIDS block specific enzymes (COX-1 and COX-2) that are
induced by inflamed tissue and also are produced by pre-cancerous polyps in the
intestine. Epidemiologic studies have shown that people who regularly take
NSAIDS (to treat conditions such as arthritis) have lower rates of colorectal
polyps, colorectal cancer, and colorectal cancer-associated mortality.
Most NSAIDs inhibit both COX enzymes, and many of these drug can also cause
other medical problems like stomach bleeding when taken regularly for long
periods of time. The reason for these side effects may be that COX-1 is
necessary for healthy mucosal tissues, but COX-2 is not. Celecoxib specifically
inhibits only COX-2, and therefore has shown little evidence of causing gastric
problems. Celecoxib is already FDA-approved for rheumatoid arthritis and
osteoarthritis.
Because FAP is such a rare disease and because this population of patients have
few treatment options, the FDA approved the limited use of celecoxib on the
basis of data from a single trial. As part of the "fast track"
review, Searle Monsanto is mandated to continue studying the drug, its safety
and efficacy, including whether or not it will ultimately provide tangible
clinical benefit for persons with FAP.
NCI is sponsoring five chemoprevention trials using celecoxib, including for
the reduction of sporadic polyps (polyps that occur in people without a known
genetic predisposition to colon disease), in hereditary nonpolyposis colon
cancer, Barrett's esophagus, bladder dysplasia, and actinic keratoses.
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