BISXINIOTIS-PIONNER OF CARDIONCOLOGY

October 7, 2010 — Growing awareness of the cardiovascular adverse effects of anticancer drugs, plus the fact that cancer patients are surviving and living longer, has given birth to the new clinical discipline of cardioncology.

Some of the new anticancer drugs are so effective that they can keep tumors in check; ironically, it is their adverse effects on the heart that can threaten to cut life short. A death from therapy-related heart failure in a patient whose cancer is in remission is the ultimate irony — a deathblow from collateral damage while the war on cancer is being won.

This imagery of collateral damage comes from an editorial introducing the special September/October issue of Progress in Cardiovascular Disease. It points out that patients with early-stage breast cancer are now more likely to die from heart disease than cancer, highlighting the need for a new discipline that focuses on the treatment of cardiovascular disease in cancer patients.

The special issue of the journal celebrates the first year of existence of the International Society of Cardioncology.

The society was launched last year at the International Symposium of the Cardiology Oncology Partnership in Milan, Italy, explained Daniel Lenihan, MD, from Vanderbilt University in Tennessee. The meeting attracted around 120 attendees. About half were cardiologists, 40% were oncologists, and the remaining 10% were "somewhere in between," Dr. Lenihan said. This year's meeting has just begun, and runs from October 7 to 9 in Nashville, Tennessee.

"The discipline of cardioncology has been evolving for about 5 years now," said Douglas Mann, MD, from the Washington University School of Medicine in St. Louis, Missouri, who coauthored the introductory editorial.

Although there had been an awareness of cardiac problems from cancer treatments for about 20 to 30 years — namely, cardiotoxicity from anthracyclines leading to heart failure and coronary disease and valvular disease from radiation, particularly when directed at the thorax, he explained — the field was jolted into life by the totally unexpected reports of cardiac damage with novel highly targeted anticancer agents.

Trastuzumab (Herceptin), the HER2-targeted antibody used in breast cancer, was the "first shot across the bow." This was the first time that cardiac damage leading to heart failure was seen outside of the anthracyclines, and it "was completely unexpected," Dr. Mann told Medscape Medical News in an interview.

Then came the reports of heart failure with the tyrosine inhibitors — initially with imatinib (Gleevec) and more recently with sunitinib (Sutent). These adverse effects were also unexpected and came as a shock to the medical community, Dr. Mann recalls. At the time, he wrote an editorial in Nature Medicine (2006;12:881-882) to highlight the problem, entitled "Targeted cancer therapeutics: the heartbreak of success."

It seems that these various novel targeted anticancer drugs act through different mechanisms, so there does not appear to be a class effect. There also does not seem to be an obvious dose–response relationship, unlike that seen with anthracyclines, Dr. Mann said.

"This puts the cardiologist in an awkward position," he continued. "These therapies are life-saving, so we are left with watchful waiting — looking out for the development of cardiac complications and then trying to treat them as they occur."

"It leaves us in a supporting role," Dr. Mann said, and this feels uncomfortable because "cardiologists are usually in the driver's seat, controlling the disease processes."

Close Partnerships With Oncologists

Caring for such patients requires close collaboration between cardiologists and oncologists, and often the involvement of internists, Dr. Mann explained. These partnerships didn't exist previously, but they are now "evolving in real-time," he added.

They are, agreed Dr. Lenihan, who coauthored an overview paper in the special issue of the journal. But he added that both sets of specialists need to realize that the new therapies have changed the game — cancer patients are now living longer, and heart disease has become a big issue.

"Convincing cardiologists that patients with cancer are, in many cases, patients with a chronic comorbidity to be managed, more like diabetes [than a] terminal disease, can be challenging," Dr. Lenihan writes in the paper he coauthored with researchers from the European Institute of Oncology at the University of Milan, Italy.

"When a cardiac patient develops an oncologic problem, the treating cardiologist often loses interest and tends to assume a defeatist attitude that may exclude the patient from other intensive treatment and/or intervention possibilities," they write.

"Conversely, when a patient with cancer develops a cardiac problem, the patient is too often excluded from first-line, more aggressive (and therefore more effective) chemotherapeutic strategies with a major impact on the cancer outcome," they continue.

Such patients can often fall "beyond the jurisdiction" of both the cardiologist and the oncologist, and not get comprehensive care from either discipline, leaving them with management that is "limited, disjointed, and often inadequate."

This is where cardioncology steps in to offer "a comprehensive approach for the management of cancer patients with cardiac diseases," they explain.

"At this moment, it's more of a concept than a hard and fast reality," Dr. Lenihan explained to Medscape Medical News in an interview. "I think that both cardiologists and oncologists need to consider where these overlaps are and how management decisions and patient care can be shared."

No Formal Training, As Yet

There is currently no formal training for cardioncology, so clinical expertise is picked up with experience, Dr. Lenihan pointed out: "You pick it up as you are trundling away on your clinical pathway."

"But these problems are becoming so prevalent that there is an increasing need to have these components in training programs, both for cardiologists and oncologists," he said.

"We're not there yet, but the problem is now probably well enough defined that some formal training is needed," Dr. Mann agreed. He noted that the Heart Failure Association in the United States, of which he is a past president, is working on white papers addressing this issue.

Another big problem in clinical practice is that there is little evidence-based data to guide treatment in these patients, Dr. Mann explained. Any patient with cancer is automatically excluded from cardiovascular clinical trials, so there is no evidence to support treatment choices. Also, it is not clear whether heart failure resulting from anticancer drug cardiac damage responds to standard management approaches in the same way as other heart failure. "We are treating these patients with approaches while not knowing whether they are effective — which is difficult," he added.

One set of guidelines has recently been published that offers recommendations for the management of hypertension that arises with drugs that block the vascular endothelin growth-factor signaling pathway. These drugs include bevacizumab (Avastin), sorafenib (Nexavar), sunitinib, and pazopanib (Votrient).

These drugs can induce very sudden and dramatic rises in blood pressure, and the guidelines set out a series of recommendations on how to manage this adverse effect. The paper focused on hypertension because it is "the most common and the easiest to address" of all the adverse effects reported for this group of anticancer drugs, the authors explain. Others adverse effects include hemorrhage, thrombosis, nephrotoxicity, and cardiac toxic effects, they add.

Dr. Mann and Dr. Lenihan have disclosed no relevant financial relationships.

Prog Cardiovasc Dis. 2010;53:80-87, 88-93. Abstract, Abstract