Select Excerpts from the Interview

Tracks 1-2

DR LOVE: Can you discuss the data that you presented at ASCO 2005 evaluating the impact of physical activity on colon cancer recurrence and survival mined from the CALGB-89803 trial of 5-FU/leucovorin versus IFL?

DR MEYERHARDT: Patients on this trial completed two questionnaires: the first one at approximately three months into chemotherapy and the second around six months after completing therapy.

We created a metric called metabolic equivalent task (MET), which is basically a measure of energy expenditure for nine different activities, such as walking, jogging or biking. For each, patients were asked whether they engaged in the activity and, if so, how often and for how many minutes.

Then we created categories of multiples of three MET hours per week. For example, sitting still for an hour is equivalent to one MET hour, or walking for one hour at two to three miles per hour each week is equivalent to three MET hours per week. The reference range was less than three MET hours per week.

We found that colon cancer survivors who engaged in at least 18 MET hours of exercise per week had approximately a 50 percent reduction in the risk of disease recurrence or mortality, or a 50 percent improvement in the disease-free survival rate, compared to those in the reference range (Meyerhardt 2006; [3.1]).

DR LOVE: How much exercise would equal 18 MET hours?

DR MEYERHARDT: Walking at a pace of two to three miles per hour for one hour six times a week equals 18 MET hours. Of course there are ways to do it more efficiently or in less time.

Jogging or running for an hour equals seven or ten MET hours, respectively. Most of the patients on the study did some combination of exercise rather than one single aerobic activity.

DR LOVE: What caveats should be considered when reviewing these data?

DR MEYERHARDT: Obviously our study was observational and we did not randomly assign patients to one level of physical activity or another. Also, one could argue that the healthier patients are the patients who are able to exercise more.

To minimize the bias from patients who were becoming sicker, we didn’t count events, recurrences or deaths within six months of the activity assessment in the primary analysis. Even extending this restriction to 12 and 24 months, we continued to observe a positive effect of exercise.

DR LOVE: What is the potential biologic explanation for your findings?

DR MEYERHARDT: One explanation is that factors like obesity and lack of physical activity increase one’s insulin levels and insulin-like growth factor, both of which have been shown to be mitogens for tumor development, metastasis and angiogenesis.

Thus, if patients avoid obesity or increase their level of physical activity, they may be decreasing those levels. If cancer recurrences result from micrometastatic disease that grows, metastasizes and develops a blood supply, then inhibiting those factors may prevent those events from occurring.

Track 3

DR LOVE: You recently published data evaluating dietary patterns and their association with colon cancer recurrence and mortality in this same CALGB trial. Can you discuss those data?

DR MEYERHARDT: A variety of individual dietary factors are related to colon cancer risk, so we utilized dietary patterns to obtain a general sense of patients’ overall dietary intake. The two patterns we used were the “prudent” and “Western” pattern diets.

A Western pattern diet is characterized by higher intake of red meat, fatty foods, sugary foods, desserts and refined grains, whereas a prudent pattern diet has a higher intake of poultry, fruits and vegetables.

Every patient was scored in both dietary patterns, and the patterns were not correlated with each other. For example, a patient may eat hamburgers every day and still eat a lot of fruits and vegetables, so although they may have a reasonable score on a prudent pattern diet, they can still score high on the Western pattern diet.

Our primary finding was related to the Western pattern diet. Patients who scored on the highest level, indicating a higher intake on the Western pattern diet, had over three times the risk of colon cancer recurrence and mortality compared to those on the lowest level of the Western pattern diet (Meyerhardt 2007; [3.2]).

DR LOVE: What is the biologic interpretation of this data?

DR MEYERHARDT: Similar to what we see with obesity and low physical activity, we know that higher levels of the Western pattern diet increase the risk of diabetes and increase people’s C peptide levels, thus modulating insulin and insulin-like growth factors. That is one possible hypothesis for how diet affects micrometastatic disease in the adjuvant setting.

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