Doctor Doctor: Giving the Heart its Due
Network - Winter 2008
The more than 10 million cancer survivors in the United States, and even some physicians, often aren’t aware of the consequences of cancer and its treatments on the heart. That’s why Jean-Bernard Durand, M.D., medical director of Cardiomyopathy Services at M. D. Anderson, and his colleagues are working to better understand hypertension and cardiotoxicity, possible late effects of treatment. Their ultimate goal is to prevent heart damage or intervene during treatment, rather than treat the problem when heart failure occurs.
What are hypertension and cardiotoxicity?
Hypertension is abnormally high blood pressure as well as the disease of which this is a symptom. Uncontrolled, it progresses to heart failure.
Cardiotoxicity is an acute or long-term injury to the heart as a result of cancer treatment, such as chemotherapy, radiation, immunotherapy, targeted therapy and hormonal therapy. When we speak about cardiotoxicity that implies the whole cardiovascular system: the arteries, the veins, the heart valves, the heart muscle or the electrical system.
What has inhibited research in this area?
Part of the difficulty with clinical trials studying heart problems in cancer patients is that we tend to work in silos. Patients with significant cardiac problems are largely excluded from cancer clinical trials while patients with a significant cancer history are largely excluded from cardiovascular trials. We have this great work in cardiology and in cancer. As we develop new therapies, our success in getting patients safely through treatment requires that we bring these two disciplines together to reduce associated cardiovascular risks.
Which drugs cause hypertension or cardiotoxicity?
For decades, one of the standard ingredients of combination chemotherapy has been a class of drugs called anthracylcines, such as doxorubicin and epirubicin. While they are effective in treating cancer, we also know they can cause cardiotoxicity.
However, in the last few years, there has been a major paradigm shift as researchers introduce new targeted therapies. While these drugs have reduced cardiotoxicity, the risk of drug-induced hypertension is significant. For example, bevacizumab (Avastin) causes hypertension in 23% to 34% of patients and is life-threatening in 14%; alemtuzumab (Campath) affects 11%; infliximab (Remicade) affects 10%; and rituximab (Rituxan) affects 6%. Others that may cause cardiotoxicity include bortezomib (Velcade), trastuzumab (Herceptin) and imatinib (Gleevec).
Can hypertension and cardiotoxicity be managed?
When heart problems occur, people get frightened. However, in many cases, they’re treatable. We’ve found a way to improve heart function, combining beta blockers, specifically carvedilol (Coreg) and metoprolol (Toprol XL), with ACE inhibitors. In addition, M. D. Anderson has integrated current guidelines from the American Heart Association and the Heart Failure Society into clinical practice.
Our most important efforts, however, are to be proactive and prevent or detect problems early. Currently, we’re investigating a blood test called BNP, brain naturetic peptide, a molecule released from the heart in times of stress. Now FDA approved to diagnosis heart failure, it may provide an excellent predictor of who will develop cardiotoxicity long before the EKG or echocardiogram becomes abnormal or symptoms develop.
While the incidence of heart failure is low, the incidence of hypertension is high. A National Cancer Institute task force is looking at how to treat high blood pressure in patients on these targeted therapies. There also is an important committee of experts in cardiology and oncology who have come together to form CONQUER, Cardiology Oncology InterNational QUest to Educate and Research Heart Failure, to begin establishing recommendations on how to improve the care of cancer patients and survivors with cardiovascular disease.