Heart & Lung Watch

Medical advances have allowed more people to survive longer after a cancer diagnosis than in years past. But in some cases, successful treatment results in heart and lung problems that do not show up for decades.

Doctors have known for years that some chemotherapy drugs take a toll on the heart and lungs. However, these same agents are responsible for prolonging life. “Some of the drugs we give for certain diseases, like lymphomas or breast cancer, can weaken the heart muscle,” says Craig Earle, MD, medical director of the Lance Armstrong Foundation Adult Survivorship Clinic and a gastrointestinal oncologist at Dana-Farber Cancer Institute in Boston. “That may not be a problem initially. But over time as people age and other things affect the heart, they can end up with congestive heart failure.”

Medications in a class known as anthracyclines can harm the heart. Adriamycin (doxorubicin), commonly given to treat breast and childhood cancers, is an example.

“It’s dose-dependent,” Earle says. “The more of the drug you have, the more likely this is to be a problem.”

For example, a cumulative dose throughout the course of treatment of Adriamycin equal to 300 mg/m2 or of its sister drug Ellence (epirubicin) at 600 mg/m2 is thought to create a higher risk.

Earle explains that anthracyclines cause the body to create free radicals that help the drug kill the cancer cells. While other cells in the body can neutralize the free radicals, the heart muscle lacks much neutralizing capacity. That leaves the free radicals available to hurt the heart muscle, leading to a weakened heart or accelerated plaque buildup in the arteries.

Combining an anthracycline with radiation, Herceptin (trastuzumab) or some other drugs adds to the danger, research has indicated. Also, patients younger than 18 or older than 65 when treatment starts have an increased risk. An underlying heart condition also increases the chance of cardiac complications.

Lee W. Jones, PhD, assistant research professor in the Department of Surgery at Duke University in Durham, N.C., suggests more attention should be paid to bringing high blood pressure or other cardiac-related conditions under control before starting cancer treatment.

Herceptin also has been associated with heart failure. The condition usually resolves after therapy ends but may persist long-term, Earle says.

Jones cautions that other drugs used to treat breast cancer, such as Avastin (bevacizumab) or aromatase inhibitors, also may have some negative cardiovascular effects.

“Those effects can be quite subtle. And we actually don’t see them right away,” Jones says. “We don’t know the long-term effects of these agents.”

Treating testicular cancer or Hodgkin’s disease with Blenoxane (bleomycin) can result in pneumonitis, which is inflammation and subsequent scarring of the lung. Rather than a late effect, it usually occurs during treatment and higher doses appear to affect risk. Older patients, those with impaired kidney function, smokers and people with an underlying lung disease have a greater chance of developing lung problems. Doctors can choose other agents for these high-risk patients.

Less data are available about long-term effects of platinum-based drugs such as cisplatin, used to treat testicular and other cancers. Cisplatin can cause damage to nerves (a condition called neuropathy) and to cells lining blood vessels. Studies also indicate the drug may increase risk of high blood pressure, lipid abnormalities, insulin resistance and obesity, which indirectly predispose people to heart attack and stroke.

Radiation presents another risk. Beams aimed at the chest to fight lymphomas, breast or

other cancers also can reach the heart and lungs. Radiation can weaken or scar the heart muscle or damage valves in the heart, research shows. Radiation also can accelerate coronary artery disease, creating rough spots in the arteries where fatty plaque can accumulate. Patients who have received such therapy may be more prone to suffering a heart attack at a younger age.

Risk factors include associated use of anthracycline therapy and having a tumor close to the heart. Patients younger than 18 or with existing heart disease or cardiac risk factors have a greater chance of developing cardiac radiation effects. A total dose to the heart of 30 Gy or a daily dose fraction of more than 2 Gy bumps up the risk, research has found.

In addition, treatment for lymphoma or breast or lung cancer may result in radiation pneumonitis. That could develop into pulmonary fibrosis, a scarring of the tissue. Years later, heart or respiratory failure may occur as a result.

“I suspect the incidence may be less than for patients treated 20 or 25 years ago.”

Current data on such late toxicities come from patients treated 10 or 20 years ago. Oncologists, more aware of those dangers today, try to keep doses strong enough to work but low enough to avoid problems.

“Regimens are designed to limit late toxicities,” Vaughn says.

Also, newer equipment allows radiation oncologists to target doses at the tumor with less fallout to other organs. Radiation specialists also try to keep daily doses equal to or below 2 Gy.

“There is still some incremental damage,” Jones says. “Radiotherapy is not benign.”

Earle is optimistic late effects will be less common in the future due to current practices. Vaughn agrees: “For the current generation of patients having treatment, I suspect the incidence may be less than for patients treated 20 or 25 years ago.”

On the other hand, Jones is more pessimistic. He thinks some of the newer agents used to fight breast cancer also may result in late heart effects. He acknowledges a lack of data suggesting a long-term risk and bases his theory on how the current drugs work: The agents may weaken the heart. The tissue might not fully recover. Yet the patient may not have symptoms. Later, those patients might be at greater risk of heart disease.

“Treatments are longer and exposures to negative effects are greater than they used to be,” Jones says.

Recently, the American Society of Clinical Oncology released a summary review of treatment late effects on patients’ hearts and lungs. An expert panel set out to develop guidelines for survivors’ care. But after reviewing the scientific data, Vaughn, a panel member, said the group discovered more research was needed.

The lack of data leaves experts with little advice to offer cancer survivors beyond the basics. People should seek regular medical care. Simple blood pressure and lab tests can pick up changes early. If the screening shows a problem, the doctor can develop a treatment plan to manage blood pressure or cholesterol levels.

Survivors should be sure to fully inform providers about their medical history. Secure a list of cancer treatments received, and share that list with any new doctor. Informed patients can remind a primary care provider about cancer treatment-associated risks and discuss whether any screenings would be beneficial.

At the same time, lifestyle changes are key in lowering heart risks: Stop smoking. Eat a healthy diet. Drink alcohol only in moderation. Maintain a normal weight. Exercise. Control blood pressure.

“All that will help,” Earle says. “There’s no downside to healthy living.”

Survivors should report to their doctors any shortness of breath, swelling or fatigue. A study by Steven Lipshultz, MD, of the University of Rochester Medical Center in New York, found many childhood cancer survivors were unaware of late-stage cardiac effects. Although the survivors felt tired during normal activities, they did not associate it with cancer treatment-related heart problems.

Vaughn, meanwhile, urges survivors not to panic. Late toxicities develop only in people who survive. Fear of late complications should not interfere with the chance of a cancer-free life.

“Patients need to be cured,” Vaughn says. “Then we need to monitor carefully. You need to practice a healthy lifestyle and be aware of the problem. Together we will face this in the future.”

“People need to be mindful of the risk,” says David J. Vaughn, MD, associate professor of medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia. However, he adds, “it should be remembered, these late toxicities are not that common.”

Certain drugs, as well as radiation to the chest, have been linked to late-effect heart and lung conditions. Both children and adults are susceptible to these complications, cancer specialists say.