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Evidence-Based Oncology June 2015
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In Conversation With a Cardiologist: Anju Nohria, MD

Surabhi Dangi-Garimella, PhD
Anju Nohria, MD, assistant professor, Harvard Medical School, spoke to Evidence-Based Oncology about some of the challenges clinicians face with monitoring cardiovascular risks in cancer patients.

Anju Nohria, MD, is assistant professor, Harvard Medical School, and a member of the Cardio-Oncology Program a collaboration between Brigham and Women’s Hospital and Dana-Farber Cancer Institute. A cardiologist by training, her area of subspecialty is heart failure and transplantation. Nohria spoke to Evidence-Based Oncology on how the Cardio-Oncology Program originated and some of the challenges clinicians face in identifying high-risk patients and monitoring cardiovascular risks.

Can you provide a brief history of the launching of the Cardio-Oncology Program?

Dr Lawrence Shulman, chief of staff at Dana-Farber Cancer Institute, and Dr Kenneth Baughman, who was the head of the cardiovascular Shapiro Center at Brigham, recognized the unmet need and together decided to develop a collaborative program. It was primarily initiated as a survivorship program, looking at late cardiotoxicities in people who had previously been treated with anthracyclines and radiation; during the course of the program, though, we recognized the cardiotoxic effects of novel chemotherapy agents as well. So it evolved into a program that looks at survivorship, cardiotoxic effects of novel agents during treatment, and taking care of patients with concomitant heart disease and cancer.

The cardiotoxic effects of anthracyclines have been known for a while; additionally, patients treated with radiation in the late 1980s or earlier were known to present with late cardiac effects. So they decided that being a big cancer center and cardiology center, we needed a program that evaluates this it was more of an administrative decision. We were not the first in the nation, though, to monitor cardiac effects of oncology treatment Memorial Sloan Kettering and MD Anderson have had [cardio-oncology] programs for a while.

What is known about the newer oncology agents and their effect on the cardiovascular system?

Several tyrosine kinase inhibitors, especially the ones that inhibit vascular endothelial growth factor, have been shown to cause hypertension. So we manage a lot of patients with concomitant hypertension while they are undergoing chemotherapy with those agents. Some of these agents, for example, sunitinib, used to treat renal cell carcinoma, have been shown in some instances to cause cardiomyopathy and heart failure. Some of the newer agents used in the treatment of chronic myelogenous leukemia have been shown to cause acute vascular events, and we are involved in the care of those patients as well. With several of the newer agents, we still don’t have enough information to predict their cardiovascular effects a few have targets that are expressed in cardiac as well as cancer cells, which may result in unwanted adverse events.

What is the demographic of the patients who participate in the program?

Older persons or those with preexisting heart conditions or cardiac disease tend to be more susceptible. This is true for late cardiotoxicity as well as for acute cardiotoxicity. For example, a 65-to-70-year-old patient with coronary artery disease will be at a greater risk of developing heart failure. Similarly, very young children, whose organs are still developing, tend to be more susceptible to the cardiotoxic effects of these treatments.

What is the duration of pediatric patient monitoring post treatment?

We follow pediatric patients quite frequently for a really long time. At the Perini clinic at Dana-Farber a survivorship clinic run in concert with Children’s Hospital pediatric cancer survivors are followed well into their 20s and 30s. What are some of the cardiovascular end points monitored during chemotherapy? Depending on what the preclinical data show either animal studies or phase 1 studies some of the drugs could be more arrythmogenic or could cause QT prolongation; so the patient’s EKG [electrocardiogram] would be monitored for arrhythmia or QT prolongation. Blood pressure would be monitored in patients administered drugs that cause hypertension. Serial EFs [ejection fractions] would be measured for drugs known to cause cardiomyopathy, such as the Her2 blockers trastuzumab, lapatinib, and pertuzumab. Most patients on these drugs end up getting ECHOs [echocardiograms] every 3 months to examine their EFs.

The oncologic community is definitely more aware and vigilant, especially when there are indications [of cardiotoxicity] from preclinical studies.

When does the cardiologist become a part of the care team of a cancer patient?

I get involved when there is a problem; I don’t see all cancer patients. I only see high-risk cancer patients or those who develop an issue following treatment.

Patient management then becomes a collaborative process I’d start the patient on cardiac medication, consult with the oncologist on whether their oncology treatment needs to continue or needs to be held till their cardiac function improves. We’d also discuss whether there’s a need to alter their oncology regimen, although the final decision is made by the oncologist. I see the patient as often as is needed. It’s a collaborative decision, because for a patient with a high-grade disease, if they are not going to be alive without the chemotherapy, you have to weigh how bad their cardiac condition is and whether it can be managed medically. It’s a conversation that depends on who the patient is.

Are medical organizations like the American College of Cardiology (ACC) or the American Society of Clinical Oncology raising awareness of cardio-oncology?

Several major meetings now include sessions on cardio-oncology; at the recent ACC meeting I was part of a half-day session that was devoted to cardio-oncology. The American Society of Echocardiography has developed independent guidelines on how to monitor patients who have been treated with anthracyclines and trastuzumab.

So although it’s still a relatively data-free zone, various organizations are working to raise awareness around this issue. What we are still lacking is a mutually acceptable set of guidelines collectively developed by cardiologists and oncologists to prospectively monitor these patients, and this is primarily because of the lack of sufficient data in the field.

How aware is the pharmaceutical industry about this issue, and what steps do they implement to manage these drug toxicities?

Drug developers are quite aware of the toxicities of chemotherapeutic agents, and they include cardiac event side effects in their adverse event reporting. Several cancer drugs have a rapid approval process because progression-free survival is an acceptable end point in cancer the criteria for approval of oncologic drugs is different, and sometimes it’s about the risk-to-benefit ratio. We have to understand it’s a different equation, because you have competing risks from 2 lethal diseases and you have to decide whether the benefit from chemotherapy will outweigh the risk of a concurrent cardiotoxic effect of the drug, which could be manageable.

So in closing, there are several novel oncology regimens being developed that could affect various organs, including the heart. Going forward, the more vigilant we are, the better we can manage these patients so we do not necessarily deprive them of essential cancer therapy.
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