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Oct 03

Cardio-Oncology: Oral medications may lead to better humancare

An Interview with Dr. Carrie Lenneman – PART 3 of 4

In June 2021, The Kinetix Group, interviewed Dr. Carrie Lenneman, a cardiologist who specializes in working with cancer patients who have a higher-than-normal risk that their cancer treatment may affect their heart. She also works with patients who have had previous cancer treatment and are experiencing symptoms that may be related to their prior treatment. Dr. Lenneman is Medical Director of the Cardio-Oncology Clinic at the University of Alabama at Birmingham (UAB), O’Neal Comprehensive Cancer Center at UAB, in Birmingham, Alabama.

Cardio-oncology is a subspecialty area of cancer care that has become increasingly important as the number of long-term cancer survivors continues to go up. Advancements in cancer therapies have tremendously improved the long-term survival of patients. However, some of the treatments can be hard on the heart, especially for those individuals who may have other medical conditions, or who have sensitivities to their therapies.

What follows is Part 3 of a transcript of our interview with Dr. Lenneman, edited for this format.

Warren Smedley: Dr. Lenneman, you mentioned the anthracyclines as the primary class of therapy that causes these toxicities. But also in the literature, radiation therapy is mentioned. And, of course, a lot of breast cancer patients typically would receive some form of radiation as a part of their therapy. The literature indicates that the cardiotoxicities from chest radiation may not show up for 10, 15, or even 20 years. What are you seeing in this regard?
Dr. Lenneman: Absolutely. Radiation can be toxic to the heart. Our radiation oncologists work hard to minimize the cardiovascular impacts. Fortunately, the technology has improved significantly over the last 30 years. I mean, from the eighties and nineties there has been great improvement. For example, we do CT acquisition so that we can minimize the field of planes of exposing the heart. We also do breath holds to minimize tissue movement. And the equipment uses much more sophisticated conformal radiation that shapes and divides the radiation into tiny beams, while the equipment moves around the body, again, to minimize dosing to non-targeted tissue.

So when I compare my breast cancer survivors from the eighties, or even my lymphoma patients that had mantle radiation to their chest, we’ve had significant improvement in decreasing in the cardiovascular toxicities. The outcomes over the last few decades have improved as we’ve improved our radiation techniques.

Also, there is the whole new field of proton therapy that is being explored. There are ongoing clinical trials looking at comparing conventional radiation for breast cancer with proton therapy, and then comparing the cardiac and vascular effects of those two different forms of radiation modality. At the moment, we think proton therapy may have less risk of cardiovascular impact, but more long-term data is needed.

Warren Smedley: You mentioned in your article promising new research using stem cells; have there been any developments there?
Dr. Lenneman: So there was the completion of a study called SENECA that I was involved in using mesenchymal stem cells that were injected into the myocardium percutaneously. That was actually a Phase 1 study to explore, “Hey, is this safe? Is this possible?” We know that with anthracycline use, patients can develop anthracycline induced cardiomyopathy, because this class of drugs causes cell death of the cardiac myocytes, and cardiac myocytes, in general, don’t regenerate. And, if they do, it’s very slowly. So the thought is that perhaps some form of regenerative medicine would help reverse this cardiomyopathy. So researchers have looked at using different kinds of cells to explore these avenues. The SENECA study used mesenchymal stem cells, and they appear to be safe. I’m not sure if it’s going to go on to a Phase 2 or Phase 3 study. These kinds of studies are very labor intensive and create a little bit of increased risk for patients, so I think there’s a lot to be determined yet. Time will tell.
Warren Smedley: Okay. A lot of the cancer therapies are shifting from the traditional infused therapy to an oral therapy. That’s great because it’s probably more convenient for the patient. We get a lot of positive feedback from patients about orals. However, Dr. Carl May wrote an article in 2014 that talks about how we’re shifting the burden of therapy and care to the patient more and more, making adherence more difficult. Where the patient used to have to come and sit down in a chair, and we, as the clinical team, would make sure they got their therapy correctly, at the right time, the right way. Now we’re sending them home and it’s harder for them to stay on their therapy correctly. Are you seeing any impact of pushing into the oral area and patients actually taking their medications incorrectly and increasing the potential for cardiotoxicities?
Dr. Lenneman: Sure. For any of us, it’s hard to remember to be a hundred percent compliant. And, often, a lot of these oral chemotherapy meds have complicated instructions. They may need to be taken at certain times or have special conditions like they need to be given with or without food, or at so many intervals from the time of having a meal. They may also have potential drug interactions that patients need to be cautious of. So it complicates things. We let them take maybe their cholesterol, their blood pressure medicines at this time, but then you can’t take your cancer medicine until so many hours lapse. So it becomes a complicated regimen. We try to set patients up for success by giving them a calendar and helping them set reminders. But it’s difficult for anyone. So, obviously, as patients miss multiple doses, there’s an increased risk that the therapy is not as effective.

One of the things I deal a lot with in our CML patients who are on an oral tyrosine kinase inhibitor, or other medications in that tyrosine kinase family, is that their response to the therapy is very dependent on how well they’re able to be compliant with those medications. And, of course, my bigger role for these patients, is to advise them about the potential cardiovascular effects. Because you’re right, when a patient is on oral therapy they are at home and don’t need to come in as frequently. They are not interacting with the healthcare system as much, so I really try to make sure that they know what symptoms they need to be on the lookout for. I do my best to make sure that they’re aware of the increased risk of these medicines for possible arterial and vascular events.

I really try to spend some time educating them about what the signs and symptoms of stroke, heart attack, and blood clots are so that they know what to do when suddenly they say, “Oh my gosh, I am having facial droop, or I’m weak on one side, or I’m having really unusual chest pain or shortness of breath.” They need to say to themselves, “I need to go to the ER. I need to talk to my physician immediately. Don’t let this continue to go on.” Patient education is another really important thing that we can do to help emphasize what the typical side effects could be and what they need to be alert to when they’re taking these oral meds. Because you’re right, they’re not interacting with the healthcare system as much, and that increases the risk of problems.

Warren Smedley: Are there opportunities to improve that educational component? Do you see things that we as healthcare systems aren’t doing well, or that we could improve?
Dr. Lenneman: Yes, in general we still have a lot to do to strengthen patient self-care. Back to the example of my CML patients, we have collaborated with our oncologists so that when any patient has more than two cardiac risk factors and is going to be on a higher risk tyrosine kinase inhibitor, they absolutely need to see us in clinic and we really spend a lot of that time on education so that they really understand that these medicines, yes, they work, but they come with some increased risks – how to be in tuned to that. And then we also really drill down on proper control of blood pressure, lipids, A1-C, and getting their diet on track. All of these are essential. We really drill down on prevention because that’s our best way to fight the potential risk of cardiovascular events that can happen with these medicines.

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