Pam McAllister attended the 2010 GI Cancers Symposium in Orlando on a C3 scholarship.
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.
February 19, 2010 at 9:10 pm, Jennifer said:
Thanks very much for drawing attention to this important topic. I hope you’ll have time to answer 2 brief questions:
1) Assuming a person is stage 4 and has had an R0 resection resulting in NED, does all of this information about recurrence apply? (Little benefit to avastin or cetuximab, yes to exercise & prudent diet.) Or do oncologists consider stage 4 disease fundamentally different even if it has been resected?
2) I thought aspirin & checking vitamin D levels (supplementing if necessary) were also proven ideas for preventing recurrence?
February 20, 2010 at 9:21 am, Kate Murphy said:
Jennifer,
The studies of prudent diet and exercise were done in stage III colon cancer patients after surgery who received chemotherapy. There are no similar studies for stage IV patients, even after complete resection of both primary and metastatic tumors.
So, we probably can’t assume that diet and exercise have a role in preventing further recurrence of stage IV colorectal cancer — but we also cannot assume that it wouldn’t. There is no evidence either way.
However, prudent diet and exercise are valuable to overall health including cardiovascular health.
So choosing a prudent diet and exercising (after talking it over with your doctor) may be a good strategy.
Although studies are being planned, there is no current evidence about the value of Avastin or Erbitux in preventing further stage IV recurrence after complete resection, although both have use in treating stage IV disease.
See the next comment for more about aspirin and calcium/Vitamin D in preventing stage III recurrence.
February 20, 2010 at 9:53 am, Kate Murphy said:
Aspirin:
Dr. Andrew Chan and his colleagues published a study in the New England Journal of Medicine in 2009 that found a 29 percent reduction in death from colorectal cancer among 1,300 patients with stage I, II, or III colorectal cancer.
Over 12 years of follow-up,15 percent of aspirin users died from colorectal cancer compared to 19 percent of non-users.
The impact of aspirin appeared to be only in those patients whose tumors expressed cyclooxygenase 2 (COX-2).
Calcium and Vitamin D
Studies of calcium to prevent colorectal cancer focus on preventing new polyps in people who have been diagnosed with adenomatous polyps — but not colorectal cancer.
Two studies randomized people with adenomas found during a colonoscopy to calcium supplements or placebos.
J.A. Baron published a study in 1999 in the New England Journal of Medicine that found a moderate reduction in new adenomas during the follow-up colonoscopy.
In 2003 Maria Grau and her team published a study in the Journal of the National Cancer Institute that found a reduction in new adenomas, but only in those people whose blood vitamin D levels were above the median (29.1 ng/mL).
Preventing new adenomas in patients who have had colorectal cancer may reduce new cancers but this is different from reducing recurrences of the original cancer.
February 23, 2010 at 12:36 pm, Marissa said:
When you attended the meeting in Orlando, was the use of Erbitux or Vectibix discussed to use it for first line CRC patients with the wild type KRAS? I am confused ecause if a patient is tested and fits into that category, can they successfully be treated with Avastin first line or should the patient be treated with the Erbitux or Vectibix?