Study of a Statin to Prevent Polyps after Colon Cancer Resection
Name of the Trial
Phase III Randomized Study of Adjuvant Rosuvastatin in Patients with Resected Stage I or II Colon Cancer (NSABP-P-5). See the protocol summary.
Dr. Bruce M. Boman (Protocol Chair), National Surgical Adjuvant Breast and Bowel Project (NSABP)
Why This Trial Is Important
Millions of Americans take drugs called statins to lower their cholesterol levels and protect against heart attacks. Statins may also protect against some types of cancer, including colorectal cancer. However, this is somewhat controversial. “While some retrospective observational studies suggest that statins prevent colorectal cancer, others do not. Moreover, most of these studies were short term and were not designed to look at tumor development; so the jury is still out on the efficacy of statins," said Dr. Boman. “What is needed is a properly designed, long-term, prospective study that evaluates tumor development, and that’s why the randomized, placebo-controlled, double-blind NSABP P-5 study was developed.” To determine the effectiveness of statins as a form of chemoprevention against colorectal cancer, NSABP researchers are testing statins in people who are at high risk of developing colorectal tumors, specifically those who have already been treated for early-stage colon cancer.
Although surgical resection alone is successful in curing most patients with early-stage colon cancer, as many as 50 percent will develop a new colon or rectal tumor (mainly adenomatous polyps) within 3 years of surgery. Adenomatous polyps are not cancerous, but they have the potential to become cancer if not removed. Some patients will even develop a second primary cancer (known as a metachronous cancer) in the colon or rectum after removal of their first, or primary, cancer. Doctors are eager to find new ways to prevent the formation of adenomatous polyps and colorectal cancers in these patients and in the general population.
Patients diagnosed with stage I or II colon cancer are eligible for this trial after they have undergone surgical treatment (resection) to remove their primary tumor. Patients may also have received post-surgical (adjuvant) therapy. Study participants will be stratified (categorized) according to whether or not they have a family history of colorectal cancer, whether they regularly take aspirin and at what dose (none, 81 mg, or 325 mg), and whether they received prior adjuvant therapy. They will then be randomly assigned to take either rosuvastatin (Crestor) or a placebo pill daily for 5 years. Participants will have physical exams every 6 months during the 5-year study period and will undergo complete colonoscopies within 180 days before randomization, and at 1, 3, and 5 years afterward. Doctors will follow the participants for the development of adenomatous polyps, the incidence of metachronous colorectal cancers, and the recurrence of their primary colon cancer.
“We’re also very interested in aspirin because we know that it has some benefit in preventing colorectal polyps and cancer. So, this study is designed to accept people who currently take aspirin as long as they agree to continue their aspirin over the course of the study,” Dr. Boman added.
Like statins, aspirin is widely used to protect the heart. The long-term use of aspirin has been shown to provide protection against the development of colorectal polyps and cancer. Since statins and aspirin are often used together, researchers are interested in exploring their ability, when combined, to prevent colorectal polyps and cancer. A recent case-control study examined the effects of a daily statin and low-dose aspirin, individually and together, on the development of colorectal tumors. The researchers found that using both drugs together reduced colorectal cancer risk more than the use of either drug alone. Consequently, one of the secondary endpoints in the NSABP P-5 trial is to see if the combination of rosuvastatin and aspirin has either additive or synergistic effects.