A combined analysis of three randomized controlled trials that compared taking aspirin to a placebo after adenomas were removed found that people who took a daily low dose or baby aspirin had almost a 20 percent lower chance of another adenoma during their next colonoscopy.  High-dose or regular adult strength aspirin reduced risk of polyp recurrence by about 15 percent.

Any aspirin reduced the risk of advanced adenomas by more than 35 percent.

Advanced adenomas include polyps over 10 millimeters or polyps that are especially risky for developing into cancer including those with significant villous features,high-grade dysplasia, or early invasive cancer.

In the three studies, over 2300 people with polyps on their initial colonoscopy were randomly assigned to aspirin or a placebo in the three studies, and 2,175 had a second colonoscopy to look for new polyps.

F. Gao and colleagues concluded,

This meta-analysis suggests that aspirin prevents recurrent colorectal adenomas among patients with a history of colorectal adenomas.

SOURCE:  Gao et al., Colorectal Disease, Volume 11, Number 9, November, 2009.

Although initial reports found no reduction in polyps or cancer in people with Lynch syndrome who took aspirin and/or resistant starch supplements, longer follow-up tells a difference story.

About five years after trial participants began taking aspirin or a placebo, differences began to emerge. Even though patients in the trial only took aspirin for four years, later followup found significantly fewer colon colon cancers among those who had used  aspirin, as well as fewer Lynch-related cancers overall.   There were almost three times as many colon cancers in Lynch carriers who took a placebo compared to those who used aspirin.

The Colorectal Adenoma/Carcinoma Prevention Programme 2 (CAPP2) enrolled over 1,000 patients worldwide who carried a mutated gene that causes Lynch syndrome in a randomized study to compare daily aspirin use with or without resistant starch supplements to placebos.  Participants in the trial took aspirin, starch supplements, or placebos for four years.  An initial report in the New England Journal of Medicine found that neither aspirin or Novolose (resistant starch) made any difference in the development of polyps or cancer.

However, when the research team contacted over 600 of the original study members again, they found that, with longer follow-up, there was a significant difference in the development of colon cancer and other Lynch-related cancers.  Six patients who had taken aspirin had colon cancer compared to 16 who didn’t use it.  There was a reduction in endometrial cancer, as well.  Overall, there were 18 Lynch-related cancers in all among the aspirin-users, compared to 31 who didn’t take aspirin during the four years of the study.

Aspirin protected the people who took it for at least 6 years after they stopped.

Participants in the trial took 600 mg of aspirin daily.

Professor John Burn, from the Institute of Human Genetics at Newcastle University in the United Kingdom,who reported the newest results of CAPP2 at the ECCO/ESMO meeting in Berlin said,

Our original design allowed for long term post trial follow-up. We have managed to track down most of those who completed the trial – around 75% of the original consent cohort – with information extending up to 10 years from randomisation. We found that, around four years after randomisation, there was a divergence in the incidence of cancers between the aspirin and placebo groups. To date, there have been only six colon cancers in the aspirin group as opposed to 16 who took placebo. There is also a reduction in endometrial cancer. This is a statistically significant result and we are delighted – all the more so because we stopped giving the aspirin after four years, yet the effect is continuing, and is directly correlated with the duration of aspirin use on the trial.

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is a type of inherited cancer of the digestive tract, particularly the colon and rectum. People with Lynch syndrome have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women carriers also have a high risk of developing endometrial and ovarian cancers.

Patients with Lynch-related cancers are often diagnosed at a younger age, and their tumors develop more quickly.

Concluding, Prof.  Burn and his team recommended,

All those at risk of Lynch syndrome related cancer should consider long term aspirin use. Plans for a large scale randomised dose finding study of aspirin in Lynch syndrome will be presented.

SOURCE:  Burn et al., European Journal of Cancer Supplements, Volume 7 Number 2, September 2009, Page 320.

Aspirin is a very interesting drug which has showed to reduce the risk of cardiovascular disease and colon cancer risk and is a great pain reliever. The mechanism of action is the inhibition of an enzyme called COX-2.

However aspirin also inhibits COX-1 which is thought to be responsible for some of its side effects such as stomach ulcers, bleeding disorders and kidney problems. Therefore major pharmaceutical companies have developed specific COX-2 inhibitors to have the great benefits but not the side effects. These drugs are known as Celebrex and Vioxx.

It was shocking to see the results from the large VICTOR trial testing Vioxx in patients with colon cancer who had successful resection and adjuvant chemotherapy. This trial enrolled 1167 patients and 23 cardiovascular thrombotic events occurred (heart attacks), 16 were in the Vioxx group and 7 in the placebo group. Statistically this was highly significant making it an estimated risk of 2.66 which means increase by 266 percent. These data were the end of the COX-2 inhibitors in the chemoprevention world.

The newest study on aspirin shows clearly that the inhibition of these enzymes may benefit patients with active disease. Dr. Chan showed in 1300 patients with colon cancer were nearly 30% less likely to die from their cancer.

How aspirin works, we don’t know. It can prevent blood clots, but COX-2 is directly involved in inflammation which can be part of cancer, and invasion and metastases. These data warrant further studies of the role of these drugs for patients with colon cancer.

I discuss and use baby aspirin  for many of my patients but also let them know about the potential risk factors. For example someone with bleeding problems or stomach ulcer or kidney function problems would be not great candidate. However for patients on Avastin I do consider aspirin to potentially reduce the risk for heart attack and strokes.

Please discuss these findings with your treating oncologists.

Photo by Mara Zemgaliete

Colorectal cancer patients with early stage disease were 30 percent less likely to die from cancer and 20 percent less likely to die at all if they took aspirin regularly after their diagnosis.

Benefit was even greater for those who began taking the medicine for the first time after their diagnosis.

However, only the group whose tumors tested positive for COX-2 (cyclooxygenase2) benefited from aspirin.  

COX-2 is an enzyme that produces inflammation and pain, and aspirin blocks its activity.  About two-thirds of colon cancers express COX-2.

Data about aspirin use was collected every two years from participants in the Nurses Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Regular aspirin use was defined as taking a 325 milligram tablet at least twice a week.

Almost 1,300 people in the two studies were diagnosed with stage I, II, or III colorectal cancer and were followed after surgery.

For all patients, regardless of COX-2 status, after a median follow-up of almost 12 years:

• 15 percent of patients who took aspirin regularly had died from colorectal cancer compared to 19 percent of non-aspirin users.
• 35 percent of aspirin-users had died from any cause compared to 39 percent of non-users.
• All patients who took aspirin were 29 percent less likely to die of colorectal cancer and 21 percent less likely to die from any cause than non-users.
• Those patients who began taking aspirin after their colorectal cancer diagnosis were 47 percent less likely to die from colorectal cancer.
• Patients with COX-2 expression in tumor tissue had a 41 percent reduction in risk of dying from colorectal cancer if they were aspirin users.
• In those without COX-2 over-expression, aspirin made no difference in risk of death from colorectal cancer.

The study team concluded,

Regular aspirin use after the diagnosis of colorectal cancer is associated with lower risk of colorectal cancer–specific and overall mortality, especially among individuals with tumors that overexpress COX-2.

Andrew Chan, MD, MPH, gastroenterologist from Massachusetts General Hospital and Harvard Medical School, who led the study said,

While previous studies by our group and others showed that aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of developing colorectal cancer, this study is the among the first to show that aspirin can also improve survival in patients who have already been diagnosed with colorectal cancers. Moreover, the benefit appeared to be especially strong among patients with cancers that express COX-2. This is an important first step toward developing targeted approaches to improving patient outcomes.

Previous research has shown that aspirin reduces the risk of new colon polyps in patients recovering from early stage colon cancer.

In an editorial accompanying the JAMA article, Alfred Neugut, MD, PhD, professor of medicine and epidemiology at Columbia University, wrote,

A major recent priority in clinical oncology has been to develop biomarkers for prognosis and to predict response specific to interventions.The specificity of the response of colorectal cancers to aspirin for patients in whom tumors over-expressed Cox-2 suggests that this potential future treatment comes with its own ready-made predictive biomarker.

There is currently no commercial test on the market that tests for COX-2 in tumor tissue.  However, testing is available at academic cancer centers and research facilities.

SOURCE:  Chan et al., Aspirin Use and Survival After Diagnosis of Colorectal Cancer, Journal of the American Medical Association, Volume 302, Number 6, August 12, 2009.

What This Means for Patients

While this is good news for people with stage I, II, or III colon or rectal cancer, it is too early to make a widespread change in how colorectal cancer is treated after surgery.

Discuss using aspirin with your doctor before using it — either on a short or long term basis.

Researchers didn’t randomly assign some patients to take aspirin and others to use a placebo or sugar pill.  Instead, they asked people in the study to tell them about how much aspirin they remembered taking every two years. There was no uniform reason for taking aspirin or uniform daily or weekly dose.

Stronger, randomized studies are important before recommendations for aspirin use for all early stage patients can be made.

Aspirin can cause bleeding in the stomach and gastrointestinal tract, sometimes serious enough to be life-threatening.

Because it may interfere with blood clotting, aspirin should be avoided  before surgery, during chemo, and before a colonoscopy.  Tell your doctors if you are taking aspirin.

Nearly 850 patients with identified Lynch syndrome were randomly assigned to receive aspirin, resistant starch, or placebos for up to four years.  After an average of two years, 141 developed either precancerous polyps or cancer (neoplasia). There was no difference in either overall neoplasia or advanced neoplasia whether patients took aspirin or resistant starch or received a placebo.

• 66 patients or 18.9 percent of 693 patients taking 600 mg of daily aspirin developed polyps or cancer compared to 66 participants or 19 percent who received a placebo.  There was also no difference in the percentage who had an advanced adenoma or cancer — 7.4 percent versus 9.9 percent.
  
• Among 727 patients, 67 participants receiving 30 grams of Novelose resistant starch (18.7 percent) every day developed neoplasia, as compared with 68 taking a placebo (18.4 percent).  There were equal numbers of advanced adenomas and cancers in the two groups.

Henry Lynch, M.D., one of the study authors, said,

Aspirin has been used clinically for some time in patients at risk of Lynch syndrome, but our study shows that patients who take aspirin for this reason are simply wasting their time. The best protection continues to be an annual colonoscopy, beginning at age 25.

Dr. Lynch first described the inherited colorectal cancer syndrome now named for him.  People who inherit one of the genes associated with Lynch syndrome have a very high risk of getting colon cancer, often at a young age.  Inherited mutations reduce the possibility that damage to cell DNA will be repaired, leading to polyps and cancer.

John Burn M.D., who led the multinational study at 43 centers, and his team concluded,

The use of aspirin, resistant starch, or both for up to four years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome.

SOURCE: Burn et al., New England Journal of Medicine, Volume 359, Number 24, December 11, 2008.