Would you like a chance to see if a new experimental treatment can reduce your risk of

• A new polyp in your colon?
• Colon cancer spreading beyond your colon?
• A new colon cancer?

Researchers at the National Surgical Adjuvant Breast and Bowel Project (NSABP) would like to talk to you about a clinical trial exploring whether a statin drug can reduce the risk of new polyps, colon cancer recurrence, or a new primary colon cancer.

In the P-5 clinical trial stage I and II colon cancer patients will be randomly assigned to take either rosuvastatin (Crestor®) or an inert placebo for five years.

What’s the thinking behind the P-5 trial?

Studies of statins and colorectal cancer risk are controversial and some conflict.

However, a study that looked back at colon cancer patients in Israel and matched them to similar people who didn’t have colon cancer found that a larger percentage of patients who didn’t have colon cancer had taken statins for more than 5 years.   About half as many colon cancer patients had taken statins (6.1 percent) as people who didn’t have cancer (11.6 percent).  Even after adjusting for other risk factors for colorectal cancer, including taking aspirin regularly, statin use reduced colon cancer risk by about 45 percent.

In addition, scientists looking at cell processes have found that statins block a protein that is important in cell growth.  Blocking its action may prevent colon cancer from spreading or polyps from developing.

Who can be part of the trial?

Stage I and II colon cancer patients who

• have finished their planned treatment — surgery or adjuvant chemotherapy.
• are no more than 1 year past their treatment.
• have had a complete colonoscopy in the past six months and all polyps removed.
• if they are taking aspirin regularly agree to continue it during the five years of the trial.
• have not taken a statin within a month of entering the trial.

Are there colon cancer patients who are excluded from P-5?

• Patients who are regularly taking NSAIDS, except for aspirin.
• Patients with familial adenomatous polyposis (FAP)
• Patients with Lynch syndrome (HNPCC or hereditary non-polyposis colon cancer)
• Have high cholesterol levels that might require them to take a statin.

Are you interested?

• Talk to your surgeon or oncologist about the NSABP P-5 clinical trial.
• Locate a P-5 trial site and contact near you.

Phase III Randomized Study of Adjuvant Rosuvastatin in Patients With Resected Stage I or II Colon Cancer

• Arm I: Patients receive oral rosuvastatin once a day for five years.
• Arm II: Patients receive an oral placebo once a day for five years.

Patients on the trial will have physical exams every six months, a colonoscopy within 6 months of starting the trial, and colonoscopies 1, 3, and 5 years to look for new polyps.

The study is double-blinded — neither patients nor their doctors will know if they are getting rosuvastatin or a placebo.

Some study patients will also be asked about their quality of life and tissue samples will be analyzed for biomarkers.

Writing in the NCI Cancer Bulletin, NSABP Protocol Chair for P-5, Dr. Bruce Boman said,

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. 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.

Pam is one of the original colorectal cancer research advocates and has been involved with research advocacy activities for well over a decade. She serves on numerous research panels and has co-authored many articles including the 2008 American Cancer Society Screening Guidelines and the ASCO Clinical Opinion on Testing for KRAS Mutations.

Here is the first of three articles she has written for C3’s Research  and Treatment News about what she learned at the Orlando meeting.

Last year we learned that Avastin® (bevacizumab) was not effective in increasing disease free survival in stage III colon cancer except for a possible small transient benefit that disappeared soon after the drug was discontinued.

Some researchers think  that any benefit would require continuous exposure to bevacizumab. Patients would need to take it for life to experience any benefit or not take it at all. Lifetime use is not practical for reasons of potential serious toxicity and cost making this an unattractive option.

Recently the trial of Erbitux® (cetuximab) in stage III patients was closed since no benefit was seen in any patient group.

With the demonstration that the addition of either anti-VEGF or anti-EGFR antibodies was without benefit, is there anything these patients can do to decrease the chances of recurrence beyond the currently used chemotherapy?

It was pointed out at the recent ASCO Gastrointestinal Cancers Symposium that patients could reduce recurrence risk by following a “prudent diet” and by exercising regularly.

A prudent diet is one that includes less fat and red meat and increases consumption of fruits and vegetables. Exercising by walking one hour a day at a regular pace or any equivalent such as walking faster for a shorter time or participating in another equivalent exercise program can reduce recurrences. The mechanism by which such interventions can kill cancer cells in patients with no evident disease is unknown. One possible explanation of how such interventions can destroy micrometastases is through an effect on the immune system but there is currently no evidence to support this.

Additional studies in stage III patients currently being planned include evaluation of the duration of treatment with the  FOLFOX regimen. The study in the US alone will not include enough patients to have sufficient power to answer the question, so this will include studies in several countries that will be analyzed together. This may present a problem if one or more of the studies are not completed for any reason. Combined studies have been attempted in the past unsuccessfully so the question of treatment duration may or may not be answered.

If a shorter duration of the FOLFOX regimen is as effective as the currently used six month duration, there should be a decrease in the development of peripheral neuropathy, a particularly unpleasant side effect of oxaliplatin treatment. While few patients have long lasting substantial neuropathy, reducing the potential for any long lasting neuropathy would be worthwhile. Reducing the duration of treatment would also increase the convenience to patients while reducing its cost.

Additionally, in the US, potential benefit of the use of celecoxib, a COX 2 inhibitor, will be examined in the same study.

• Hormone replacement therapy reduces risk of colon cancer.
• Smoking before age 30 increases chances that colon cancer will recur.
• Low CEA levels improve both survival and disease-free survival for stage II colon cancer.
• Most patients want videos of their colonoscopies and are willing to pay for them.

Use of hormone replacement therapy reduces colon cancer

Women in a study of California teachers who were taking hormone replacement therapy (HRT) after menopause had a 36 percent reduced risk of colon cancer over ten years than women who weren’t on HRT at the beginning of the study.  Risk reduction was even greater for women with a first-degree relative who had colon cancer.  Their risk fell 55 percent.

Over 57,000 women were part of the study, about 60 percent of them on HRT at the study start.  Over the next ten years, 444 got colon cancer.

Despite the reduction in colon cancer in the study, doctors caution women about using HRT because of raised risks for breast cancer, heart attack, stroke, and blood clots.  Advice is to use the lowest dose for the shortest time to offset severe menopausal symptoms.

Katherine DeLellis Henderson, PhD, reports the study results in the February 15, 2010 issue of the American Journal of Epidemiology.

Early smoking history reduces disease-free survival after colon cancer

Patients with stage III colon cancer who had a smoking history of 12 or more pack years before they were 30 had almost a 40 percent increased risk of having their cancer return within three years compared to patients who had never smoked.

Among the 1,045 study participants, 46 percent had never smoked, 44 percent were past smokers, and 10 percent were currently smoking.

Disease-free survival three years after treatment was about 18 percent greater for people who had never smoked than for past smokers.

The results, based on questionnaires filled out by patients in the CALGB 80893 adjuvant chemotherapy trial, were published by Nadine Jackson McCleary, MD, MPH,and her colleagues in Cancer, February 15, 2010. They wrote,

Total tobacco usage early in life may be an important, independent prognostic factor of cancer recurrences and mortality in patients with stage III colon cancer.

CEA levels before surgery important for stage II prognosis

Patients whose CEA (carcinoembryonic antigen) blood levels before surgery were low — below 5 ng/ml — had significantly better overall and disease free survival than those whose CEA’s were 5 or higher.  For those with low CEA, overall survival at five years was 81.7 percent compared to 69.9 percent for high CEA.  Disease-free survival was 82.4 percent for low CEA and 70.6 percent for CEA that was 5 ng/ml or higher.

However, CEA levels only made a difference in stage II patients.  There was no significance for stage I or III.

Writing in the Journal of Surgical Oncology, Korean surgeon Jung Wook Huh, MD and colleagues concluded,

Preoperative serum CEA is a reliable predictor of recurrence and survival after curative surgery in patients with colon cancer, particularly in those classified as having stage II disease.

Patients want videos of their colonoscopies

Eight out of ten patients having colonoscopies said that they would like to have a video recording of their colonoscopy, and more than 6 of 10 (63 percent) were willing to pay for it.  After reading a brief paragraph explaining missed lesions during colonoscopy, over half (54 percent) were more interested in a video and none were less interested.

Meghana Raghavendra surveyed 248 outpatients at the Indiana University School of Medicine and reported the results in the World Journal of Gastroenterology, in an early online article January 28, 2010.

While overall patients with stage I or IIA colon cancer (early stage) have a lower risk of cancer returning than patients with stage IIB or III (later stage), careful surveillance after surgery is as effective in finding and treating cancer in both groups.

About one in three patients in both the early and late stage who had a recurrence detected during surveillance were able to have surgery with the goal of curing their cancer.  

Using information from the Clinical Outcomes of Surgical Therapy (COST) study, researchers divided 872 patients without metastatic colon cancer into two categories:

• Early stage disease: stages I or IIA
• Late stage disease: stages IIB and III

All patients in the study, no matter their stage at diagnosis, followed the same surveillance plan after surgery.

• History and physical exam every 3 months for 1 year then every 6 months to 5 years
• Carcinoembryonic antigen (CEA) blood test every 3 months for 1 year then every 6 months to 5 years
• Chest x-ray every 6 months for 2 years then every 1 year to 5 years
• Annual colonoscopy if positive for polyps or cancer; exam every 3 years if first one was negative
• CT scan of abdomen at discretion of physician for symptoms, signs, or increased CEA

Results found:

• By five years, about 1 in 10 early stage patients had a recurrence of their cancer (9.5 percent) compared to about 1 in 3 late stage patients (35.7 percent).
• Sites where cancer had spread were similar in both groups, although late stage patients were more likely to have spread to more than one site.
• Median survival after surgery for recurrence, when possible, was 51.2 months for early stage and 35.8 months for late stage patients.

There was little difference between groups  in how the recurrence was initially found:

• Elevated carcinoembryonic antigen (CEA) test found 29 percent of early versus 37 percent of late stage recurrent cancers and was the most common way of finding recurrences, particularly in the second year when it found more recurrences than CT-scan, chest x-ray, and colonoscopy combined.
• CT-scans uncovered 24 percent of early versus 26 percent of late stage recurrences.
• Chest x-rays found 7 percent of early versus 12 percent of late stage recurrence.
• Colonoscopy found 13 percent of early versus 9 percent of late ones.

Of the entire group of 537 patients with an early stage diagnosis (stage I and IIA), 55 had a recurrence.  20 of them went on to a second surgery and had a median survival of 51 months after their operation.  Those for whom surgery wasn’t possible had a much shorter survival of about 9 months.

There were 254 patients initially diagnosed as late stage (stage IIB and III).  Of those, 91 experienced a recurrence and 32 were able to have a second surgery.  Like the early stage patients, a second surgery led to much longer survival — 36 months versus 11 months without surgery.

Vassiliki L. Tsikitis and the study team concluded,

Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.

SOURCE: Tsikitis et al., Journal of Clinical Oncology, Volume 27, Number 22, August 1, 2009.

Recent studies have clearly shown that diet is directly associated with the risk of tumor recurrence. People who eat primarily a Western diet are significantly at higher risk than those patients whose diet has less red meat, processed sugar, desserts, and French fries. You can change your diet and reduce your risk of tumor recurrence.

You can change not only what you eat, but also how much you exercise. Daily exercise, such as walking for one hour, can reduce your risk by 50 percent — more than any chemotherapy can. For patients who are obese, weight loss will not only reduce risk for diabetes or heart disease but also decrease your risk of colon cancer.

Exercise, diet, and weight loss go along with significant changes in your body. Our immune response and reaction to stress, response to inflammation and tumor will all change the better shape our bodies are in. Every environmental change will impact the biology in our bodies. We need to strengthen our bodies to fight off the cancer. These studies show clearly that diet and exercise can easily do that.

Other data also show that taking aspirin every day can reduce the risk also by 50 percent.

All this is in your power. Please discuss these with your oncologist. In my own practice we stress the point of weight loss and exercise as well as diet.

To collect all this information I set up my blogs (go and check out the former blogs on Revolution Health). I did not want to stress out my patients writing down all this information for them, so I created these blogs where that they can go to anytime  and check out what to eat, what exercise to do, what supplements may help,whether to drink alcohol or not, whether to have sex or not . . .

Patients who ate the most red and processed meats, refined grains, fats, and sugars were about three times as likely to die or have their cancers recur as patients who ate these foods the least. While there is no shortage of evidence linking the so-called Western diet to an increased risk for developing colon cancer, the study by the group at Harvard is among the first to examine the impact of such a diet on survival among patients treated for the disease.

We should not ignore these data and make sure that our patients are aware how important diet is to reduce the risk of tumor recurrence. From my own experience, patients always ask what they can do to decrease their risk. They want to know what they should be eating and whether they should be exercising.

The “Western” diet is characterized by high intakes of red and processed meats, sweets, refined grains, and desserts. Diet defined by the researchers as “prudent” was high in fruits, vegetables, poultry, and fish. Colon cancer recurrences or death were nearly 3.5 times more common among patients who most closely followed a Western diet than among patients who followed it the least.

In our clinic we suggest that a diet characterized by higher intakes of red and processed meats, sweets and desserts, french fries, and refined grains should be avoided since it can increase the risk of cancer recurrence and decreases survival.

There are now many more good reasons for eating a diet rich in fruits, vegetables, and whole grains and limiting red and processed meats, refined grains, fats, and sugars.