Leading expert in colorectal cancer treatment, Dr. David Kerr, MD, explains how low-dose aspirin can prevent relapse after initial therapy, particularly for patients with a specific PIK3C gene mutation. He details the importance of the tumor microenvironment and discusses ongoing clinical trials in Oxford that aim to confirm the role of aspirin as a precision medicine tool in colorectal cancer care.
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Using Aspirin to Prevent Colorectal Cancer Recurrence: A Precision Medicine Approach
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- Aspirin for Colon Cancer Recurrence Prevention
- COX Inhibitors in Cancer Therapy
- Risk-Benefit for Cancer Patients
- PIK3C Mutation and Aspirin Efficacy
- Aspirin Dosing in Clinical Trials
- Future of Aspirin Research
- Importance of a Second Opinion
Aspirin for Colon Cancer Recurrence Prevention
Research indicates that aspirin, a common non-steroidal anti-inflammatory drug (NSAID), may play a significant role in preventing colorectal cancer recurrence. Dr. David Kerr, MD, a leading colorectal cancer expert from Oxford, emphasizes that the tumor microenvironment is as crucial as the cancer's genetics. Influencing the inflammation around a tumor with agents like aspirin can modify its clinical behavior and reduce the risk of the cancer returning after initial surgery and chemotherapy.
COX Inhibitors in Cancer Therapy
Aspirin works by inhibiting the COX-1 and COX-2 enzymes. Dr. David Kerr, MD, was involved in clinical trials investigating both aspirin and selective COX-2 inhibitors, such as rofecoxib (Vioxx) and celecoxib (Celebrex), for adjuvant colorectal cancer treatment. The trial involving Vioxx was halted prematurely due to cardiotoxicity concerns that arose from its use in arthritis patients. Dr. Kerr believes the risk-benefit profile is vastly different for cancer patients facing a potential recurrence, a perspective he discussed with Dr. Anton Titov, MD.
Risk-Benefit for Cancer Patients
The context of medication use dramatically alters its risk-benefit calculus. Dr. David Kerr, MD, explains that while cardiotoxicity risks from COX-2 inhibitors were significant for the general arthritis population, they might be considered acceptable for colorectal cancer patients seeking to prevent a deadly recurrence. This is a fundamental principle of oncology, where the seriousness of the disease justifies managing more substantial treatment side effects.
PIK3C Mutation and Aspirin Efficacy
Emerging evidence suggests the benefit of aspirin may be confined to a specific subgroup of patients. Work from Harvard, later confirmed by Dr. David Kerr, MD, and his team in Oxford, shows that aspirin's protective effect against colorectal cancer recurrence is likely most potent in patients whose tumors harbor a mutation in the PIK3C gene. This mutation is present in approximately 15% of colon cancer cases, paving the way for a precision medicine approach.
Aspirin Dosing in Clinical Trials
Based on this genetic insight, a new clinical trial is being planned in Oxford. Dr. David Kerr, MD, describes a study where Stage 2 and Stage 3 colorectal cancer patients with the PIK3C mutation will be randomized to receive either a 100 mg low-dose aspirin or a placebo daily. While Dr. Anton Titov, MD, inquired about the potential for a dose-effect relationship, the current trial design uses a standard low dose to establish efficacy first.
Future of Aspirin Research
Dr. David Kerr, MD, refers to this work as "teaching old medications new tricks." The future of aspirin in oncology depends on a deep understanding of molecular biology to select the right patients for therapy. He agrees with Dr. Anton Titov, MD, that further research with multiple dosing arms would be valuable to determine if a higher dose could amplify the protective effect against cancer recurrence.
Importance of a Second Opinion
This evolving field underscores the critical importance of obtaining a second opinion for advanced colorectal cancer. A second opinion confirms the accuracy and completeness of the diagnosis and ensures the treatment plan incorporates the latest advances, such as genetic testing for mutations like PIK3C. This process gives patients confidence that they are receiving the best possible personalized medicine, which may one day include targeted chemotherapy combined with aspirin.
Full Transcript
Dr. Anton Titov, MD: Aspirin can be used to prevent relapse in colorectal cancer after initial treatment. When should aspirin be used for treatment of Stage 2 and Stage 3 colorectal cancer? PIK3C mutation and treatment of colon cancer with aspirin. Colon cancer aspirin therapy.
Cox-1 and COX-2 inhibitors can treat colon cancer and prevent recurrence of colorectal cancer after treatment.
Dr. David Kerr, MD: Leading colorectal cancer expert from Oxford discusses aspirin use in therapy of colon cancer. Aspirin helps to prevent colon cancer, but it can also treat colon cancer. Aspirin affects the environment around the colorectal cancer tumor.
Dr. Anton Titov, MD: A clinical trial is using aspirin to prevent relapse of stage 2 and stage 3 colorectal cancer. PIK3C mutation and aspirin treatment of colon cancer. Colorectal cancer aspirin treatment options. Advanced colon cancer targeted chemotherapy combined with aspirin.
A second opinion confirms that a colorectal cancer diagnosis is correct and complete. It also confirms that a cure of colon cancer is possible, even in advanced colon cancer.
Dr. David Kerr, MD: The best treatment for advanced colon cancer with metastatic lesions might include low-dose aspirin. A second opinion helps to choose precision medicine and the best targeted chemotherapy plus aspirin for treatment of colorectal cancer.
Get a second opinion on advanced colorectal cancer and be confident that your precision medicine cancer treatment is the best.
Dr. Anton Titov, MD: Best colorectal cancer treatment center for personalized medicine. Video interview with a leading expert in metastatic colorectal cancer treatment from Oxford. Colon cancer aspirin therapy. Aspirin prevents recurrence of colon cancer.
The 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 the New England Journal of Medicine about the risks and benefits of COX-2 inhibitors for colon cancer therapy. This was before Vioxx was withdrawn from the market.
What is your current thinking about the use of non-steroidal anti-inflammatory agents in the treatment of colon cancer and rectal cancer? How should aspirin be used in colon cancer?
Dr. David Kerr, MD: 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 four or five years, I have realized that the microenvironment of the tumor is as important for treatment results as the genetics of the cancer itself.
Sometimes we can influence the degree of inflammation within a colon cancer tumor. Then we may be able to modify the colorectal cancer tumor's clinical behavior.
Aspirin is an inhibitor of COX-1 and COX-2 enzymes. 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 a COX-2 inhibitor reduce the recurrence of colorectal cancer? This would be after the surgical resection of the colon cancer tumor and after adjuvant chemotherapy was done.
In our large clinical trial, Vioxx (rofecoxib) was withdrawn because of worries about its cardiotoxicity. This was done prematurely, in my opinion.
For colorectal cancer patients, the risks of cardiotoxicity from Vioxx or Celebrex are relatively trivial. 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. A very serious side effect was discovered, but side effects were managed successfully, considering the seriousness of the disease.
How should we interpret the risks of medication for different patients? Side effect risks for the general population or in cancer treatment have different meanings.
Dr. David Kerr, MD: I absolutely agree with this statement. COX-2 inhibitors (Vioxx, Celebrex) were developed for arthritis patients. These are non-steroidal anti-inflammatory medications.
This is a very different patient profile than colon cancer patients. They are at risk of cancer returning. The risk-benefit ratio for cancer patients is very different than that for arthritis patients.
Colon cancer patients are more likely to take greater risks with the treatment. Patients with a sore knee or sprained ankle will take less risk of side effects.
Dr. Anton Titov, MD: There is a lot of good epidemiological and observational data. It suggests that aspirin can prevent colon cancer from developing.
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 the 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.
Dr. David Kerr, MD: We repeated excellent work by our colleagues at Harvard. This work shows that the benefits of aspirin in colon cancer 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. We are proposing a clinical trial for colorectal cancer patients who have a mutation in the PIK3C gene.
We will randomize colon cancer patients to receive aspirin or placebo prospectively. We would like to demonstrate if, in some patients, aspirin can prevent relapse and recurrence of colon cancer. The expected effect is in 15% of colon cancer patients.
Dr. Anton Titov, MD: What doses of aspirin are you using in this clinical trial? For the prevention of cardiovascular events, there are very different dosages of aspirin used in various clinical trials.
Dr. David Kerr, MD: We are using low-dose aspirin, 100 mg per day. But you are absolutely correct. There is a controversy about aspirin dosing.
We need more money, more patients, and more time for a clinical trial. Then we would probably ask this question.
Dr. Anton Titov, MD: What is the best aspirin dose in cancer recurrence prevention? I would like to have three study arms to see if there was a dose effect.
This is my understanding of the clinical evidence and molecular pharmacology of aspirin. I don't think that there is a dose-effect relationship between aspirin dose and its effects.
Dr. David Kerr, MD: We have to choose one dose. Then we would choose a low-dose aspirin (100 mg per day). But there is a benefit to looking 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. It is widely available. Aspirin can probably make even a small difference in the recurrence rate of colon cancer. Then it will mean a lot for colon cancer patients.
Dr. David Kerr, MD: I absolutely agree. We say it's "teaching old medications new tricks." Knowing the molecular biology of colon cancer is crucial. Selecting patients for appropriate colon cancer therapy is then possible.
We will have to see if we can amplify the potential of using aspirin to treat colon cancer.
Dr. Anton Titov, MD: That would be a great story. I hope we can demonstrate the positive effects of aspirin on colon cancer recurrence. Colon cancer aspirin therapy can be effective. Aspirin changes the microenvironment of the tumor.
Leading colon cancer expert (Oxford) on aspirin cancer therapy. Aspirin can be used to prevent relapse in colorectal cancer after initial treatment. When to use aspirin for Stage 2 and Stage 3 colorectal cancer adjuvant treatment? PIK3C mutation and treatment of colon cancer with aspirin. Leading colorectal cancer expert from Oxford discusses aspirin use in therapy of colon cancer.