February 25, 2000

Colorectal cancer awareness efforts target aspirin

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Dr. Raymond DuBois

Colorectal cancer awareness efforts target aspirin

Colorectal cancer is a cancer no one wants to talk about, despite that it is the second leading cancer killer — claiming more than 56,000 Americans this year — and it is 90 percent curable if caught early.

Throughout the month of March, a national effort, spearheaded by NBC's Katie Couric and anti-cancer fund-raiser Lilly Tartikoff, is aimed at making people talk about this disease, how to fight it and how to prevent it. Couric and Tartikoff, along with the Entertainment Industry Foundation, have formed the National Colorectal Cancer Research Alliance (NCCRA), which is dedicated to raising awareness about the disease and support research into better ways to detect it, cure it and prevent it.

Dr. Raymond DuBois, Vanderbilt-Ingram Cancer Center's associate director for cancer prevention, is one of seven leading colon cancer researchers involved in this effort, which will kick off its public campaign with a press conference next week in New York City.

"Colorectal cancer usually starts as a small polyp, or growth, inside the colon or rectum," DuBois said. "Not all will become malignant, but if we can detect these and remove them early, that will eliminate them before cancer occurs. Unfortunately, fewer than half of all Americans over the age of 50 have ever been screened for the disease as recommended."

Congress has officially designated March as Colorectal Cancer Awareness Month, and as part of this initiative, the VICC will host a free Colon Cancer Prevention Forum, presented by DuBois at 10 a.m., Saturday, March 4. The event at the Wild Oats in Green Hills will include healthy cooking demonstrations, recipes and other tips on preventing colorectal cancer.

Among the exciting ideas for preventing this disease comes from more than a decade of research that has suggested aspirin and other non-steroidal anti-inflammatory drugs might play a role in preventing colorectal cancer. Now, DuBois and his colleagues at the VICC and three other institutions are planning to put that idea to the test with the first large study of a new aspirin-like drug in patients at risk of developing colon cancer.

"The potential to save lives is great if we can develop a drug that will prevent these cancers safely," said DuBois, a co-investigator in the national study. "As people age, their risk for developing colon cancer increases, so with an aging population, the impact of such a prevention strategy will be even greater over the next couple of decades."

DuBois, Mina Cobb Wallace Professor of Cancer Prevention and director of Gastroenterology at Vanderbilt, is recognized as a leader in the research over the past 10 years that has associated aspirin use and a reduced risk of colon cancer. A few years ago, he and his colleagues helped pinpoint the culprit — an enzyme called cyclooxygenase 2 (COX2) that is one of the targets for aspirin and other NSAIDs. DuBois and his team found that elevations of COX2 are increased in colon cancer and that tumors shrink when this enzyme is blocked by agents that inhibit it.

However, aspirin and NSAIDs were feared to be too harsh on the stomach to use as a "chemoprevention" for colon cancer. The gastric side effects result because aspirin and NSAIDs also block another enzyme known as COX1, a chemical that protects the stomach lining from irritation.

The recent development of more selective COX2 inhibitors, which do not block COX1, has opened the door for testing the drugs as a potential colon cancer prevention agents. DuBois and his VICC colleagues have assisted in a study of one of these drugs, celocoxib, in patients with an inherited form of colon cancer. The FDA recently approved use of the drug for patients with that form of the disease, and the drug has also been approved for use as an anti-inflammatory in patients with rheumatoid arthritis.

This new study would be the first to test the drug's prevention potential in a much larger group of patients who represent the more typical American at risk of developing the disease. Colorectal cancer occurs in about 130,000 Americans each year and is the third most common cancer among men and women. More than 56,000 deaths are attributed to colorectal cancer each year.

The study, called the Polyp Prevention Trial, is planned to enroll about 3,000 patients who have had a polypectomy (surgical removal of colon polpys) in the previous three months. It is known that these patients are at increased risk for developing additional polyps and that, if left alone, these polyps will transform over time into tumors.

Eligible participants will have had:

•A one-centimeter colon polyp removed;

•Two smaller polyps removed;

•Or one smaller polyp removed and a history of colorectal cancer in the family.

Its design calls for patients to be randomly assigned to take regular doses of celocoxib or a dummy pill (placebo). A year later and again in two more years, each patient would undergo a colonoscopy to assess whether they have developed additional polyps. "We plan to compare the size and number of polyps in each group to see if use of the drug makes any difference," DuBois said.

Centers participating in the National Cancer Institute-funded study also include Johns Hopkins, Wake Forest and Cornell universities. As many as 20 additional sites may be added in the future, DuBois said.

DuBois and team of VICC scientists have also received a $5 million, five-year grant from the NCI to continue their basic research looking more precisely at how these drugs play a role in cancer prevention. The ultimate goal of their work is to identify potential other targets for chemopreventive agents that might be more effective and/or safer to use than the first group of selective COX2 inhibitors.