Cardio-Oncology

Dr. Tara Lin: Welcome to Bench to Bedside, a weekly series of live conversations about recent advances in cancer from the research bench to treatment at the patient's bedside. I'm Dr. Tara Lin, Medical Director of the University of Kansas Cancer Center, Clinical Trials Office and Director of the Acute Leukemia Program, sitting in for Dr. Roy Jensen. My guest today is Dr. Charles Porter, a heart failure cardiologist and Director of Cardio-Oncology at the University of Kansas Health System. Thanks to advances in cancer treatment, the number of cancer survivors is growing and expected to exceed 20 million in the U.S. by 2026. New therapies are helping patients live longer but that also means many patients will need ongoing therapy and that therapy can cause heart problems over the long term. This has led to the field of cardio-oncology and the need for ongoing management of cardiotoxicity in cancer patients. Dr. Porter, what is cardio-oncology and why is this area of specialty growing?

Dr. Charles Porter: Well cardio-oncology is the collaborative care of patients undergoing or having undergone cancer treatment that have cardiac problems or vascular problems related to their treatment.

Dr. Lin: What is cardiotoxicity and what are the causes?

Dr. Porter: Well cardio-toxicity actually has been around since 1967 when the first drug that caused heart failure was released called Adriamycin and that continues to be an active agent in cancer treatment, and you can consider it the Tom Brady of cardiotoxic chemotherapy and in Kansas City, we know Adriamycin is like Tom Brady. He seems like it's been around forever, and he's still causing problems for us. We haven't solved all those problems yet but we're working on 'em very hard. And that was the seed, the emergence of Adriamycin in 1967 was the seed for cardio-oncology. It started to grow 30 years later when a drug called Herceptin or Trastuzumab became the first targeted therapy for breast cancer and that drug caused off-target effects including heart failure or weakening in the heart that was not anticipated when the drug was released. The difference in Adriamycin and Herceptin was what spawned cardio-oncology in the early days because Herceptin interfered with treatment during the patient's cancer attack by the doctors, and it would interfere by weakening the heart before the patient who had straightforward cancer, breast cancer, had completed their year of therapy and in patients with metastatic disease who would need ongoing therapy indefinitely. A weakening heart could interfere with the ability to give Herceptin, which in many cases was the only reasonable drug to use for cardiotoxicity for cancer in spite of the cardiotoxicity. And the field really exploded in this century as new targeted agents for a multitude of cancers that are increasingly released without big trials because the cancers are so bad and they have off-target effects that hurt the heart and blood vessels. And the ability for a cardiologist to understand what's going on with the drugs and understand where the treatments are serious and how you can modify the cancer, allow the cancer treatment to not be modified and still protect the patient from heart and vascular disease is critical because you can't just stop a cancer drug like you can tell someone with alcoholic cardiomyopathy to stop drinking. People don't want to die of their cancer with the comforting feeling that they died five years early, but their heart was fine. They want to survive and that's what we're doing is to help people get through their cancer treatments and continue to live normal lives when the toxicity might last longer than the treatment itself. We have to work with the cancer docs to collaborate on what's important, what's not important and how I can deliver therapy for heart problems without becoming such a burden on the patient that they can't manage the cardiovascular tests and treatments in a way that doesn't interfere with their cancer treatment.

Dr.  Lin: If you're just joining us, we're talking about cardio-oncology and how to manage a cancer patient's risk of cardiotoxicity. Pauline Horton is here in the studio to take your questions. Remember to share this link with people you think might benefit from our discussion. Use the hashtag, #BenchToBedside. Dr. Porter, what types of cancer treatments are linked to heart problems and why?

Dr. Porter: Well that's an increasingly difficult question. Ten years ago, 15 years ago, you'd say, Well Adriamycin," which is one of the drugs you use a lot and that is still a very, very commonly used drug and it has high potency against some terrible cancers. Breast cancer, not as much as it used to be, but acute leukemias, lymphomas, Hodgkin's Disease in young people, sarcomas sometimes affecting teenagers or small children are among the key agents. But here, it's still used in a lot of different areas and then now with breast cancer being first treated as a targeted cancer in the late 1990s, but now these new targeted agents and many of these are the ones you see on TV where you're specifying a very genetically determined type of non-small cell lung cancer. Those are all targeted therapies. They target the cancer and not the entire patient. And that's been a dream since Paul Erlich won the Nobel Prize in medicine in 1908, said he was trying to invent, develop a magic bullet that would attack the cancer and not attack the patient and that's what's being fulfilled with these targeted therapies. Non-small lung cancer, gastric cancer, Herceptin's used with gastric cancer, multiple myeloma, malignant melanoma. President Jimmy Carter is alive today, disease free with no evidence of metastatic melanoma because of targeted therapy. His did not affect his heart, but there are combinations of drugs used for his condition that can cause myocarditis in a manner that we hadn't previously seen with anything. So there's a growing list for those of you who might be dealing with someone with Waldenstrom Macroglobulinemia, if you can say it. That's also a targeted therapy. All these drugs are released generally speaking with smaller trials and less understanding about what's gonna happen when you give it to 5000 people on little trials that may be 6 to 900, because these drugs are fast tracked. So people like Jimmy Carter don't die while the drug is still waiting for 10000 patients to be treated.

Dr. Lin: Are some patients at higher risk for developing cardiotoxicity from their treatments?

Dr. Porter: Absolutely and that's one of the things that comes into play with Adriamycin, because the first reports of Adriamycin were in children with cancer was leukemia, and that was in 1967. The first report on toxicity for heart failure with the drug came in 1973, six years later. And even then, the suggestion was that older age group is more vulnerable and this is why if you're a young child getting Adriamycin, you will get a dose that's 500 mg/m2, it's a measure lifetime dose that's based on your body surface area, but 500 mg/m2 is well tolerated in a seven year old, but in a 60 year old with a lymphoma, it's virtually a guarantee for heart failure. So you have to adjust the dose back depending on the age of the patient. Preexisting heart disease is a problem, risk factors for coronary disease, diabetes, those risk factors are all added into the equation of what's the likelihood of toxicity, particularly with Adriamycin. Some of these other drugs again, it's called a multiple hit theory. It hasn't really been proven, but your heart has only has so much of a tolerance for different toxins. So if you've had Adriamycin, if you've had in the old days, chest radiation for breast cancer, hit the heart now it doesn't, if you're going to the right place, which I think is most places now. So you can mitigate some of these risk factors and other things for coronary disease, develop later, more commonly in people who have had breast cancer treatment. Postmenopausal women with breast cancer are more likely once they've had initial good response, more likely to die of cardiovascular disease complications than they are of recurrent breast cancer. So it's a total game changer from 30 years ago when almost every cancer was a death sentence, and you know, if you've got cancer, you can say, "Well you can eat steak, you don't need to worry about a low fat diet, 'cause you're hasta la vista." But now, people are playing for the long term. The five year survival rate for women with most breast cancers is over 80%, approaching 90%. Prostate cancer, five year survival is way over 90%, but these therapies they have increased the risk for coronary disease, so we have to watch those and be aware of them.

Dr. Lin: What questions should patients ask their oncologist either when they're getting ready to start treatment or at some time during their treatment course?

Dr. Porter: Well I think a good question to ask and it's not necessarily when you're in shock about cancer, you're not backing off and saying, "What about heart disease?" You first have to get over the shock that you're not going to die of the cancer and that there is a future in front of you and you can just ask, "Is this treatment likely to hurt my heart or increase my risk of having heart problems during therapy or after?" And the oncologist know about these toxicities and you know oncologists are some of the world's best primary care doctors because once you've got cancer, your primary care doctor's gonna say, "Woo, better see your cancer doctor about that." So you have to deal as a cancer specialist with osteoporosis in women, metabolic abnormalities on cancer clinics. I come back after clinic and go back and check the inpatients and one patient would have a low calcium that's threatening their life and another will have a high calcium and this is all after hours work. So there's a huge amount of work that cancer doctors know which drugs ... You know which drugs and cardiotoxicity, you mentioned that, you've probably never given Adriamycin to someone without having mentioned heart disease. The problem is some of these drugs, we don't even know what's developing, particularly the new drugs. When you have a very serious illness, it's nice to get a new therapy when all the other therapies are terrible. But you don't really know what the toxicity is and sometimes when you're going out with these cancer drugs, these early drugs, it's like going out into the field and eating mushrooms. Well, you find out which ones are bad by seeing whose sick at night and the next night and say, "Now what did Mikey eat?" You know? And some of these toxicities are like that. You just keep an eye on what's out there and the main thing I think that's important for a cancer specialist and patients to realize is there are cardiologists who focus on this area and their eyes don't glaze over when they look at a cancer treatment record and they can actually pick out the hidden, you have to know the little abbreviations and you change 'em. So that you have to know what's going on with the patient and understand the therapies in order to just read the chart and figure out what to tell the patient.

Dr. Lin: Now do all cancers have a cardio-oncology program like we have at the University of Kansas? Dr. Porter: No, and it all depends on what the program is. You can ... Hat's off to KU's marketing program and those other programs in town because I think every hospital system in Kansas City Health System and in Kansas City can brag about having a world class marketing department. So there are probably, and no health system wants to say, "No we don't have that." So you can say that. We have probably one of the most established and robust programs in the country. I was at a cardio-oncology session in London this fall and they showed a map of the first 10 cardio-oncology programs in the country and KU was one of those 10. So that, was nice. I've been involved initially, with a hat's off to Carol Fabian in breast cancer. She brought me in with Jennifer Klemp to get started with this more than 10 years ago and we really have a robust program and on the cancer specialists, are learning that they're not in it alone and that it helps. I think a lot of them prefer to contact me then just send the patient to any cardiologist, 'cause I really do understand what's going on in their cancer treatment.

Dr. Lin: If you're just joining us, we're talking about how clinicians identify and manage cardiac related side effects from cancer therapies. With newer therapies coming to market quickly and cancer survival rates increasing, long-term cardiac issues can be a problem for many survivors. Pauline Horton is here in the studio to take your questions. Any final questions Pauline?

Pauline Horton: We have no questions at this time, but we will be watching the conversation throughout the day so if you have any questions after the broadcast ends, just leave them in the comments below.

Dr. Lin: Okay. So we've been talking about cardiac toxicity from cancer treatments, and the take home message that I'm getting from you is that cancer patients should be concerned. As we discussed that initial shock of having cancer once that phase sort of passes, you're saying it's important for patients to ask questions of their doctors about what those long-term risks could be and how to manage them.

Dr. Porter: That's true, but the main thing to take home from this is that there is no reason to fear taking a life-saving or life-prolonging cancer therapy for fear of cardiotoxicity. Take the drugs, keep in touch. I mean I saw a patient yesterday who was at risk for cardiovascular disease and she googled cardio-oncologists and she told my nurse that she came up with the fact that I was the only cardiologist in the state of Kansas with any identifiable activity in this area. You don't necessarily need to do that, but you need to work with your oncologist to see if there are risks that can be mitigated and get the right testing. This particular patient in Wichita was having echo studies that were more complicated then was needed because you don't need all the possible echo imaging techniques to monitor for toxicity. So in her case, I was able to simplify her treatment by cutting out a lot of the components of an echo that are not necessary in long-term surveillance for Herceptin toxicity.

Dr. Lin: Any final thoughts or comments you want to share with our viewers today? Dr. Porter: I don't think so.

Dr. Lin: Okay, all right. Thank you Dr. Porter and that's it for today. Next week, your voice and opinion is needed more than ever. Please join us as we talk about how cancer research is determined in large part by the needs of patients, survivors and caregivers. Learn how your voice can be heard and helps to focus research initiatives. That's right here next Wednesday at 10 a.m.