New discipline of cardioncology evolves as cancer patients now live longer

Zosia Chustecka

October 08, 2010

Nashville, TN - Growing awareness about cardiovascular side effects of anticancer drugs, plus the fact that cancer patients are now living longer, has given birth to the new clinical discipline of cardioncology.

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

This imagery of collateral damage comes from an editorial introducing the September/October 2010 issue of Progress in Cardiovascular Disease s, dedicated to the management of cardiac disease in cancer patients. It also points out that patients with early-stage breast cancer are now more likely to die of heart disease than cancer, highlighting the need for a new discipline that focuses on the treatment of cardiovascular disease in cancer patients.

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

The society was launched last year at a meeting in Milan, Italy, explained Dr Daniel Lenihan (Vanderbilt University, Nashville, TN). This was the Third International Symposium of the Cardiology Oncology Partnership, and it attracted around 120 attendees. About half were cardiologists, 40% were oncologists, and the remaining 10% were "somewhere in between," Lenihan said. The 2010 meeting started this week in Nashville and runs through October 9.

"The discipline of cardioncology has been evolving for about five years now," said Dr Douglas Mann (Washington University School of Medicine, St Louis, MO), who coauthored the introductory editorial [1].

Although there had been an awareness of cardiac problems from cancer treatments for about 20 to 30 years—especially cardiotoxicity from anthracyclines leading to heart failure as well as 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, Genentech), the HER2-targeted antibody used in breast cancer, was the "first shot across the bow," the first time that cardiac damage leading to heart failure was seen outside of the anthracyclines, and it "was completely unexpected," Mann said in an interview.

Then came the reports of heart failure with the tyrosine inhibitors, initially with imatinib (Gleevec, Novartis) and more recently also with sunitinib (Sutent, Pfizer). These side effects were also unexpected and also came as a shock to the medical community, Mann recalls. At the time, he wrote an editorial in Nature Medicine to highlight the problem [2].

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

"This puts the cardiologist in an awkward position," he continued. "These therapies are life-saving, and 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," Mann commented, and this feels uncomfortable as "cardiologists are usually in the driving seat, controlling the disease processes."

Close partnerships with oncologists

Caring for such patients needs close collaboration between cardiologists and oncologists, Mann commented, and internists are also often involved. These partnerships didn't exist previously, but they are now "evolving real-time," he added.

They are, agreed Lenihan, who coauthored an overview paper in the special issue of the journal [3]. But he also 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 as opposed to terminal disease can be challenging," Lenihan writes in the paper he coauthored with researchers from the European Institute of Oncology at the University of Milan, Italy [4].

"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, without getting 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," Lenihan commented 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 no formal training for cardioncology at present, so the clinical expertise must be gained from experience, Lenihan commented: "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," Mann agreed. He noted that the Heart Failure Society of America, 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, Mann commented. Any patient with cancer is automatically excluded from cardiovascular clinical trials, and so there is no evidence to support treatment choices. Also, it is not clear whether the heart failure resulting from anticancer drug cardiac damage responds in the same way as other heart failure to standard management approaches. "So 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 endothelial growth factor (VEGF) signaling pathway [5].

These drugs include bevacizumab (Avastin, Genentech), sorafenib (Nexavar, Onyx Pharmaceuticals/Bayer HealthCare Pharmaceuticals), sunitinib, and pazopanib (Votrient, GlaxoSmithKline).

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 the side 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 groups of anticancer drugs, the authors explain. Others adverse effects include hemorrhage, thrombosis, nephrotoxicity, and cardiac toxic effects, they add.

Mann and Lenihan report no conflicts of interest.

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