Wednesday, May 31, 2017

colorectal cancer staging radiology









colon cancer aspirin treatment. aspirin prevents recurrence of colon cancer. dr. anton titov, md: use of non-steroidal anti inflammatory agents (aspirin) in colorectal cancer treatment and prevention is one of your interests. experience with selective cox-2 inhibitors has been mixed. you wrote in new england journal of medicine about the risks and benefits of cox-2 inhibitors for colon cancer therapy. it was before vioxx was withdrawn from the market. what is your current thinking about the use of non-steroidal anti-inflammatory agents - like aspirin - in treatment of colon cancer and rectal cancer? dr. david kerr, md (colon cancer oncologist, oxford): as we've discussed i spend a large amount of time working with colleagues in oxford. we study the molecular genetics of colorectal cancer cells within the tumor. but over the past 4 or 5 years i have realized that microenvionment of the tumor is as important for treatment result as the genetics of the cancer itself. if we can influence the degree of inflammation within a colon cancer tumor, we may be able to modify colorectal cancer tumor's clinical behavior. aspirin is an inhibitor of cox-1 and cox-2 enzymes, and rofecoxib (vioxx) and celecoxib (celebrex) are selective cox-2 inhibitors. we were very interested to ask this question in a clinical trial: would aspirin or cox-2 inhibitor reduce the recurrence of colorectal cancer after the surgical resection of colon cancer tumor and after adjuvant chemotherapy? in our large clinical child vioxx (rofecoxib) was withdrawn because of worries about cardiotoxicity of rofecoxib . this was done prematurely, in my opinion. for colorectal cancer patients risks of cardiotoxicity from vioxx or celebrex are relatively trivial. so we could not recruit enough patients into that clinical trial. dr. anton titov, md: this situation is analogous to what we saw in multiple sclerosis with tysabri, when very serious side effect was discovered but nevertheless managed, considering the seriousness of disease. so it's different how to apply the risks of medication for general population vs. in the cancer treatment.


dr. david kerr, md (colon cancer oncologist, oxford): i absolutely agree with this statement. cox-2 inhibitors (vioxx, celebrex) - non steroidal anti inflammatory agents - were developed for arthritis patients. this is a very different patient profile than colon cancer patients at risk of cancer returning. risk - benefit ratio for cancer patients is very different that for arthritis patients. colon cancer patients are more likely to take greater risks with the treatment than patients with sore knee or sprained ankle. there is a lot of good epidemiological and observation data suggesting that aspirin can prevent colon cancer from developing. and in those patients who have developed colorectal cancer, aspirin can reduce the risk of cancer returning. there is a large clinical trial in the uk that looks at adjuvant use of aspirin for stage 2 and stage 3 colorectal cancer treatment. we are planning a clinical trial in oxford that will use precision medicine. we have done colorectal cancer treatment work in oxford that repeated excellent work by our colleagues at harvard. this work shows that benefits of aspirin in colon cancer maybe may be confined to those patients who have a mutation in a gene called pik3c. we repeated this work and showed exactly the same result as our harvard colleagues. so we are proposing a clinical trial for colorectal cancer patients who have a mutation in pik3c gene. we will randomize colon cancer patients to receive aspirin or placebo prospectively. we would like to demonstrate if in some patients, about 15%, aspirin can prevent relapse and recurrence of colon cancer. dr. anton titov, md: what doses of aspirin are you using in this clinical trial? because for prevention of cardiovascular events there are very different dosage of aspirin is used in various clinical trials. dr. david kerr, md (colon cancer oncologist, oxford): we are using low dose aspirin, 100 mg per day. but you are absolutely right - there is a controversy about aspirin dosing. if we heard more money, more patients and more time, we would probably ask this question about aspirin dose and would have three study arms to see if there was a dose effect. based on my understanding of the clinical evidence and molecular pharmacology of aspirin, i don't think that there is dose effect relationship between aspirin dose and its effects. if we have to choose one dose we would choose low-dose aspirin (100 mg per day). but there is a benefit to look at different doses of aspirin in colon cancer treatment, i agree with that.


dr. anton titov, md: aspirin is a medication that is not expensive. aspirin is widely available. if aspirin can make even a small difference in the recurrence rate of colon cancer, it will mean a lot for colon cancer patients. dr. david kerr, md (colon cancer oncologist, oxford): i absolutely agree. we say it's "teaching old drugs new tricks". knowing molecular biology of colon cancer, selecting patients for appropriate colon cancer therapy. we will have to see if we can amplify the potential of using aspirin to treat colon cancer. that would be a great story if we can demonstrate the positive effects of aspirin on colon cancer recurrence.










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