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ANNOUNCER: The fight against cancer may have some new weapons. Doctors are finding that the painkillers called COX-2 inhibitors, could have the ability to prevent or treat some cancers. While the research is on-going, the current news about COX-2 inhibitors is optimistic. But just what are COX-2 inhibitors?
DAVID JOHNSON, MD: There are at least two enzymes, COX-1, cyclooxygenase 1, and COX-2, cyclooxygenase 2.
COX-1 is present in most cells of the body and it's very important for the normal function of cells, such as kidney cells, gastrointestinal cells. COX-2 on the other hand is an inducible enzyme. That is, various events cause that particular enzyme to become active. COX-2 is probably responsible for the inflammation that one experiences with arthritis, for example, or for injury.
ANNOUNCER: Traditionally physicians would treat arthritis and many types of pain with aspirin or a non-steroidal anti-inflammatory drug.
DAVID JOHNSON, MD: These drugs inhibit COX-1 and COX-2. Motrin, the drug that you might buy at the store, or Advil is a typical NSAID. And the COX-2 drugs target specifically COX-2, turning it off. And does not affect COX-1.
ANNOUNCER: The COX-2 inhibitors now on the market are the popular arthritis and pain medicines, Celebrex, Vioxx and Bextra.
RAYMOND DUBOIS, MD, PhD: Right now they're mainly being used in patients who have rheumatoid or osteoarthritis. And they're used for symptoms of pain and management of symptoms associated with joint pain and chronic inflammation.
ANNOUNCER: But scientists have found that high levels of COX-2 are also present in many cancers. So disrupting COX-2 with an inhibitor, may improve the treatment process of various diseases. Scientists are using COX-2 inhibitors in higher doses than normally used in the treatment of arthritis, to study their anti-cancer effects.
ANDREW DANNENBERG, MD: There are a number of possible uses for COX-2 inhibitors in the prevention and treatment of cancer. Possibilities include colorectal cancer, lung cancer, breast cancer, bladder cancer.
ANNOUNCER: There are several ways that COX-2 inhibitors can potentially affect cancerous tumors.
RAYMOND DUBOIS, MD, PhD: One is that they cause an inhibition of the cells to proliferate, so the cells can't grow as fast as they normally do. These inhibitors stimulate the cells to undergo programmed cell death, so that the cells die at a more rapid rate. Thirdly these coxibs seem to inhibit the process of blood vessel growth into the tumor. We call this tumor-induced angiogenesis: it's a big word, but basically it's just the ability to provide nutrients through the blood supply to the tumor.
ANNOUNCER: Researchers feel COX-2 inhibitors could also play a role in the prevention of certain cancers.
ANDREW DANNENBERG, MD: In individuals who are at increased risk for a cancer, one might envision a COX-2 inhibitor being prescribed. So for example, in a patient who has had a colorectal polyp, a pre-cancerous lesion in the colon, one might envision a compound such as a COX-2 inhibitor being used after that polyp has been removed to attempt to prevent the recurrence of the disease.
ANNOUNCER: COX- 2 inhibitors are also being studied as possible treatment options for patients who already have cancer.
ANDREW DANNENBERG, MD: There have been two trials that I'm aware of which have been completed to date. One involves patients who have familial adenomatous polyposis or FAP. These patients will develop colorectal cancer by the age of 50 if their colons aren't removed. The study which involved Celebrex, demonstrated definitively that Celebrex could decrease the number of colorectal polyps and this led to its approval by the FDA; adjunctive therapy for the treatment of FAP.
In a trial that we just completed we took patients with a diagnosis of non-small cell lung cancer. A common treatment is preoperative chemotherapy. We added Celebrex to that regimen and then patients went to surgery. We have results that we consider to be quite promising, and future studies are planned to better define the utility of selective COX-2 inhibitors in this particular patient population.
ANNOUNCER: One of the advantages of COX-2 inhibitors is they seem to have fewer side effects and can be given in much higher doses, than similar drugs.
RAYMOND DUBOIS, MD, PhD: There've been two well designed randomized studies that have been completed-the CLASS trial and the VIGOR trial and they both show that selective COX2 inhibitors have about a 50% reduction in side effects that NSAIDS cause in the GI tract.
ANNOUNCER: The use of COX-2 inhibitors represents the newest approach in the war against cancer, which may be beneficial in both prevention and treatment.
RAYMOND DUBOIS, MD, PhD: With the treatment of cancer, usually in the past we wait until we are presented with a patient who has a full-blown tumor that's already developed in the body and then we use a very toxic regimen to try to kill those tumor cells, and in the process we kill normal cells as well. What we're hoping with the coxibs and the approach using these kinds of drugs is it could be considered a more preventive approach.
ANDREW DANNENBERG, MD: In all likelihood, if COX-2 inhibitors prove to be useful in the treatment of cancer, they will need to be given in conjunction with other standard therapy. You don't wake up one day with cancer. There is a disease process, which takes many, many years. Medical science needs to focus more on prevention and try to develop medications that will be useful in preventing invasive disease. So in this case, a COX-2 inhibitor is a very rational choice to try to intervene early in the disease process before cancer develops.
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