Cancer prevention by medications. Aspirin and COX-2 inhibitors delay cancers and Alzheimer’s disease. 5

Aspirin might be a magic bullet to prevent diseases. Because today there are three major catastrophes: ischemic heart disease, cancer, Alzheimers disease. Most probably aspirin can prevent or delay all three major health catastrophes. Leading oncologist and cancer prevention expert.

Let’s talk about chemoprevention of cancer. How to use medications to lower risks of cancer? Dr. Anton Titov, MD. How to use medicines to lower chances of cancer return? Dr. Anton Titov, MD. If cancer had already been diagnosed and treated. You did important work on cancer chemopreventive methods. That included aspirin use in chemoprevention of gastrointestinal cancers. Could you please tell us how aspirin helps to reduce risks of gastrointestinal cancers? Dr. Anton Titov, MD. What are the potential mechanisms of cancer prevention by aspirin? Dr. Anton Titov, MD. And it’s quite controversial. Aspirin for cancer prevention actually is not controversial. There is a long history and lot of data about aspirin in cancer prevention. But aspirin must be used in the correct way. Obtain medical second opinion on cancer. Then it can prevent not only colon cancer but many other cancers. Aspirin was first marketed in 1897. It was more than 120 years ago. Aspirin is still prescribed. I think that aspirin might be the magic bullet for cancer prevention. I feel strong about aspirin for cancer prevention because this is an old medication. Dr. Nadir Arber, MD. We know a lot about aspirin efficacy and toxicity, so I feel safe about it. This is another important point. When a patient comes to me, he doesn’t tell me this. “I don’t mind to die tomorrow from anything as long as it is not lung cancer, colon cancer or heart disease.” Patients come in and say that. “Dr. Nadir Arber, MD. We would like to live longer and better”. Dr. Anton Titov, MD. This is a big mistake. During clinical clinical trials for cancer chemoprevention and early detection of cancer everyone does this mistake. They are using one organ as target of clinical cancer prevention clinical trial. This is a mistake because you should look for overall morbidity and mortality. You should not look at only one specific organ. I’m going to tell you momentarily about a big clinical trial where I was a principal investigator. Dr. Nadir Arber, MD. We used the COX-2 inhibitors to prevent colon cancer. Dr. Nadir Arber, MD. We had amazing results. Aspirin might be a magic bullet to prevent many types of cancer. Because today there are three major catastrophes. It is ischemic heart disease, cancer, and Alzheimers disease. And most probably aspirin can prevent or delay these three major catastrophes. Dr. Nadir Arber, MD. We know the profile of aspirin side effects is low. Even if there is major bleeding we know as gastroenterologists how to prevent bleeding. But bleeding due to aspirin is quite rare. Especially we should treat Helicobacter Pylori. Obtain medical second opinion on cancer. Then side effects are avoidable. Helicobacter pylori is an important risk factor. It can increase risks of side effects. But H. Pylori can be easily identified by a diagnostic test. Helicobacter pylori can also cause gastric cancer. Exactly! Dr. Anton Titov, MD. I think aspirin should definitely be taken for cancer prevention. I personally take it and I think this is the way to go. It’s true that genetic profile is also important to reduce aspirin risks. Dr. Nadir Arber, MD. We also published paper about genetic influence on cancer prevention. How we can predict the response to non-steroidal anti-inflammatory cox-2 inhibitors based on data from our genome. Now we are trying to validate it in a large number of samples. But this is going to be the way forward. Somebody will be prescribed aspirin or a novel medication. Obtain medical second opinion on cancer. Then we’ll make sure that the patient doesn’t carry a mutation for high side effects risks. Dr. Anton Titov, MD. In 1999 Merck and Pfizer came to the market with a new medication. It’s COX-2 inhibitors. There are two COX enzymes in our body. COX-1 is the housekeeping gene. It keeps the integrity of the gastrointestinal mucosa by keeping its integrity. COX-1 is housekeeping gene. It’s constantly expressed in the entire gastrointestinal mucosa. COX-2 is not expressed in normal mucosa. But it is upregulated as a consequence of inflammatory or neoplastic cancer-inducing stimuli. Dr. Anton Titov, MD. Merck and Pfizer came out with this COX-2 inhibitors that inhibit only COX-2. They did not inhibit COX-1. This in theory should be the preferred medication. That is not going to hamper or damage the normal [gastric] mucosa, because it does not inhibit the expression of COX-1 But at the same times it can treat inflammation because it inhibits COX-2 which is over-expressed in inflammation. At that time I came to Merck and Pfizer. It was before they were acquired by Pfizer. This medication was owned by Pharmacia. I told them. Whenever you want to have a new medication, first you look for toxicity. If the drug is not toxic, then you look for efficacy. Now you have a perfect medication. Because you have checked it in so many patients. It’s not toxic. And it’s very effective in controlling pain and inflammation. Why don’t we try to find the new indications. Let’s see if  COX-2 inhibitors can also prevent cancer. Dr. Anton Titov, MD. Merck said, “excellent idea, we’ll do it by ourselves”. But Pfizer let me and Professor Bernard Levine do it. At that time, Professor Bernard Levine was at MD Anderson hopistal. He was a professor emeritus from Tel Aviv University. Dr. Nadir Arber, MD. We did an international multicenter clinical trial. It spanned the entire world. It had 1561 patients from five continents, 107 medical centers across the world. Dr. Nadir Arber, MD. We gave this medication, COX-2 inhibitor, to patient with colon polyps. Dr. Nadir Arber, MD. We were able to show that after 3 years and after 5 years we were able to reduce the numbers of colon polyps by roughly 50%. Dr. Nadir Arber, MD. We reduced especially advanced adenomas. Advanced adenomas are more prone to develop into colon cancer. There were two other parallel clinical trials at the same time. And they were stopped due to unpredictable and foreseen cardiovascular toxicity. Because everyone had concerns about GI toxicity. But they found some cardiovascular toxicity. But this is strange because the number of patients were very low. Sometimes we speak with cardiologists. They tell me about cardiovascular toxicity when you’re talking about thousands of patients. Not a few dozen patients, or even less that we had. Dr. Nadir Arber, MD. We had about 19 and 31 with heart toxicity of COS-2 inhibitors. It’s very low. Obtain medical second opinion on cancer. Then also side effects became evident after a year or 1,5 years. It was only in patients who had some risk factors. These patients had had ischemic heart disease. Dr. Anton Titov, MD. With these patients you should be more careful and be more conservative. But other patients did well. It was true especially for patients with high risk for colon cancer. COX-2 inhibitor is an ideal medication to prevent colorectal cancer in hit-risk patients. But cancer prevention indication of COX-2 inhibitors was put on hold. It was based on not medical or scientific reasons. Unfortunately we can’t use this effective medication anymore for cancer prevention. There is not many other chemopreventive medications that are in wide use to prevent colon cancer. It’s probably for liability reasons. They were worried that somebody might sue them. Dr. Anton Titov, MD. Chemoprevention of cancer is certainly a very important topic.