Cancer Drugs Can Cause Heart Damage

Some Doctors Do Not Fully Protect Against Complications

Any cancer drug can cause potential heart damage, even death, and many doctors do not adequately monitor their patients or manage their care to minimize the health risk, according to a study by M. D. Anderson cardiologists.

"Patients and doctors may not be aware of the spectrum of heart problems that can arise from cancer treatment, or know that many of these problems can be managed," says the study's lead author, Edward T. H. Yeh, M.D., professor and chairman of the institution's Department of Cardiology.

The study, published in the June 29 issue of the journal Circulation, is the first large-scale review that details:

• Cardiovascular complications that often occur in cancer therapy
• Ways to prevent or treat heart problems resulting from cancer treatment

Conducted with nine other M. D. Anderson cardiologists, the study reviews research on the cardiotoxicity (toxic effects on the heart) of 29 anti-cancer drugs as well as 30 years of experience at M. D. Anderson.

Cardiotoxicity can occur in any patient, Yeh says. Generally speaking, however, patients most at risk are elderly and have other illnesses, such as diabetes and heart disease. Heart problems can occur during treatment or months and even years after treatment.

Potential problems described for each drug

Even the newest targeted therapies, designed to attack only cancer cells, can cause cardiotoxicity, Yeh says. The following potential problems can exist with these cancer medications:

Monoclonal antibodies- These substances locate and bind to cancer cells and can be used alone, or to deliver drugs, toxins, or radioactive material directly to tumor cells.

Toxic effects of these drugs (Avastin, Erbitux, and Rituxin) include:

• Hypertension (high blood pressure)
• Hypotension (low blood pressure)

"They seem to have more general toxicity than many other agents, but the problems they produce usually involve changes in blood pressure, which can be easily treated if recognized," Yeh says.

The monoclonal antibody Herceptin is less toxic than generally believed, although it can cause:

• Chronic heart failure
• Dysfunction of the left ventricular, the main chamber of the heart that pumps blood to the body

Chemotherapy drugs- Heart problems are relatively rare in the "antimicrotubules" class of chemotherapy drugs, of which Taxol is a member. However, several other common classes of chemotherapy drugs can cause potential heart damage:

Anthracyclines/anthraquinolones- (adriamycin). These agents are clearly more toxic to the heart than other medications, especially in large doses. They should be closely monitored because they frequently produce:

• Irreversible chronic heart failure
• Left ventricular dysfunction

"This is probably the most problematic class of anticancer drugs, but with experience, cardiotoxicity can be limited,"Yeh says.

Alkylating agents- Platinol and Cytoxan, the most widely used alkylating agents, can produce a wide range of heart problems at higher doses, including:

• Chronic heart failure
• Hypertension

Antimetabolites- (which include the widely used agent 5-fluorouracil). Antimetabolites can produce ischemia, a decreased flow of oxygenated blood to an organ due to an obstruction in an artery, which can lead to heart attacks if not treated.

Non-chemotherapy drugs- Potential heart damage also can occur with:

• Interleukin-2 - which frequently results in:
• • Hypotension (low blood pressure)
  • Arrhythmias (irregular heartbeat)
• Gleevec - which can cause heart failure
• Trisenox - which can result from fatal "QT prolongation" (lengthening of the part of the heart rhythm cycle referred to as the QT interval.)
• Thalidomide - which can produce a variety of serious heart ailments

Yeh says although the potential for heart damage from cancer drugs is present, complications can be avoided with proper measures.

Possible solutions include:

• Avoiding certain drugs
• Lowering drug dosages
• Administering drugs slower and over a longer period of time
• Monitoring cardiac health more stringently
• Avoiding giving some drugs simultaneously
• Treating cardiac risk factors
• Use of an echocardiogram during and after cancer treatment
• Treating patients with heart failure drugs

"We found a profile of cardiotoxicity for the most often used anticancer drugs, but it is important to know that every patient has different risk factors that will determine how their hearts handle the treatment," Yeh says. "Monitoring and management is key to surviving cancer with a good and lasting heart."