Jamie Spencer

At the dizzying moment when a patient           	              first receives a diagnosis of cancer, the side effects           	              of treatment to fight the disease may seem insignificant.           	              That was certainly true for Adriana Jenkins, who           	                found out in 2001 at age 31 that she had inflammatory           	                breast cancer and the disease had already spread        	                to her lymph nodes and chest wall.

“Quite honestly, my situation was so           	                dire,” she says now, “if they had said           	                hydrochloric acid would help, I’d have spread           	                it all over my body.” Instead, she entered a           	                trial for Herceptin® (trastuzumab). But after           	                12 weeks of treatment, despite her cancer responding           	                well, she had to withdraw from the trial because           	                of potentially dangerous changes in her heart rhythm. 

While many side effects of traditional           	              chemotherapy are well-known, such as nausea, hair loss           	              and fatigue, other problems associated with targeted           	              cancer agents, including those affecting the heart,           	              may be much more serious. Drugs can prevent or reduce           	              the severity of cardiac toxicity, and advancements           	                in anticancer therapy are attempting to lower the        	                  risk even more.

The heart is the body’s workhorse,           	              pumping blood throughout the circulatory system to           	                bring oxygen and other nutrients to tissues and organs.           	                When the heart is healthy, its four chambers coordinate           	                to keep blood flowing through the valves into the           	                blood vessels, all while its electrical system keeps           	                the heart pumping in a steady rhythm.

But when the heart is damaged           	              by certain types of cancer treatment, disturbances           	                can occur. The           	                effects can be acute, occurring shortly after the           	                start of treatment or months after the last dose,           	                or late, occurring years after treatment is over.           	                And unlike the more visible side effects of treatment,           	                such as hair loss, heart side effects are often silent,           	              though symptoms can include shortness of breath, dizziness,        	                  irregular heartbeat or swollen feet or ankles.

“The old adage ‘do no harm’ doesn’t           	                always work in the treatment of cancer,” says           	                Michael Ewer, MD, a cardiologist at M.D. Anderson           	                Cancer Center in Houston. “Some cancers have           	                to be treated aggressively, and the price we pay           	                sometimes is a cardiac effect.” 

Only a small percentage of patients who undergo           	                drug therapy or radiation experience cardiac toxicity,           	                and the percentage and severity can vary with different           	                drugs. When discussing cardiac toxicity, doctors say           	                it’s important for patients to understand the           	                difference between a cardiac event, which can be           	                a minor degree of injury that produces no symptoms,           	                versus serious heart damage that can lead to congestive           	                heart failure or other dangerous heart conditions.

Cardiac toxicity was recognized as early as           	                1967, when reports surfaced of heart failure in children           	                who received Adriamycin® (doxorubicin) to treat           	                leukemia. Since then, other cancer therapies have           	                been recognized as potentially harmful to the heart.

Drugs known as anthracyclines, which include           	                Adriamycin as well as Cerubidine® (daunorubicin),           	                Idamycin® (idarubicin) and Ellence® (epirubicin),           	                are known for their potential cardiac toxicity. Anthracyclines           	                treat a variety of cancers, including breast cancer,           	                sarcoma, lymphoma and leukemia. While serious heart           	                damage is rare in patients receiving anthracyclines—ranging           	                from 2 to 7 percent&mdash;the risk increases with           	                each dose, so oncologists carefully monitor a patient’s           	                total anthracycline dose received over a lifetime           	                to minimize the risk of permanent heart damage. Other           	                heart-toxic drugs often used in combination with other           	                cancer drugs are  5-fluorouracil, or 5-FU, and           	                cisplatin.

The old adage ‘do no harm’ doesn’t                               always work in the treatment of cancer. Some cancers                               have to be treated aggressively, and the price we pay                               sometimes is a cardiac effect. 

And then there is Herceptin, a targeted drug           	                used to treat the 25 to 30 percent of breast cancer           	                patients with HER2-positive breast cancer. While           	              Herceptin works well to reduce breast cancer recurrence           	              and risk of death, studies have shown anywhere from           	              1 to 11 percent of women who take the drug experience           	                symptomatic congestive heart failure. Investigators           	                who reported the 11 percent statistic clarified in           	                their study, published in late 2006 in the 

Journal           	                of Clinical Oncology

, that the elevated percentage           	                wasn’t surprising since a significant number           	                of patients had a history of heart disease, prior           	                anthracycline exposure and prolonged exposure to           	                Herceptin (an average of 21 months).

“There is a concern that if patients           	                develop heart trouble [on Herceptin], they might need           	                to limit something that can help them,” says           	                Charles Geyer, MD, director of Breast Medical Oncology           	                at Allegheny General Hospital in Pittsburgh who investigated           	                the cardiac toxicity of Herceptin. But there are ways           	                to optimize its benefits, he says, and although some           	                therapies carry heart-toxic risks, their cancer-fighting           	                benefits may tip the scales. “We don’t           	                want people to be afraid of Herceptin.”

In addition to drug therapy, radiation           	              directed at the chest, spine or upper abdomen may cause           	              cardiac injury. But changes to methods of delivering           	              radiation in recent years, such as using lower doses           	              and reducing exposure to heart tissue, have reduced           	              the risk.

Certain pre-existing health problems           	              can increase the risk of heart damage. People with           	                heart disease, high blood pressure, diabetes or who           	                are either very young or elderly are at increased           	                risk. All of these factors must be weighed when making        	                  decisions about treatment.    

With so many cancer patients surviving long           	                after treatment, the enduring consequences of therapy           	                have become more of a concern. “We           	                didn’t used to have long-term cancer survivors,” says           	                Carolyn Runowicz, MD, chair of the National Cancer           	                Advisory Board and director of the Neag Comprehensive           	                Cancer Center at the University of Connecticut Health           	                Center in Farmington. “It’s been an evolution.”

In addition to strategies to reduce           	              the dose of radiation to heart tissue, reducing the           	              overall dose of medication or administering the drug           	              differently can cut the risk of heart problems. With           	              Adriamycin, giving the drug by a continuous infusion           	              rather than in a large single dose can reduce its toxic           	              effects.

When Dr. Runowicz faced decisions about her           	                own breast cancer treatment in 1992 when she was in           	                her early 40s, she questioned whether she should take           	                Adriamycin. “There were not a lot of data yet           	                about the benefits of Adriamycin on survival, so we           	                didn’t know the effect,” she says. “But           	                I decided I’d rather have heart disease at 60           	                than be dead at 45 or 50. In my mind, it was worth           	                it.”

Fifteen years later, new drug formulations           	                can lower the risk of complications. A form of Adriamycin           	                called liposome-encapsulated doxorubicin, or Doxil®,           	                appears to reduce cardiac toxicity by enveloping           	                the drug within a bubble of fat, allowing it to be           	                slowly released. This allows a higher dose to be           	                given with less severe side effects.

Heart-protective drugs have been developed           	                to reduce the harmful 	effects of therapy. Zinecard® (dexrazoxane)           	                has been shown to lower iron levels in the blood,           	                reducing the level of free radicals that can damage           	                heart tissue. Zinecard also allows more patients           	                to be treated with extended doses of Adriamycin.

Another approach to protect the           	              heart from therapy involves ACE inhibitor medications,           	              such as enalapril, typically given to people with high           	              blood pressure or heart failure. These drugs slow the           	              progression of left ventricular dysfunction that results           	              from some chemotherapies.

Patients receiving potentially           	              cardiotoxic cancer therapy should be carefully monitored           	              both during and after treatment. An echocardiogram           	                (heart ultrasound) is the primary tool used to monitor           	                heart health, but other tests may also be done, including           	                blood tests, electrocardiograms or multiple-gated           	                acquisition (MUGA) scans, which produce a moving           	              image of the heart muscle.

M.D. Anderson Cancer Center’s department           	                of cardiology recently sponsored a panel discussion           	                of oncologists and cardiologists to discuss how to           	                best monitor a patient’s heart function. Concerning           	                the issue of whether to use non-invasive echocardiogram           	                or time-consuming yet generally more precise MUGA,           	                the panel determined either imaging method was acceptable           	                depending on the expertise of the radiologists and           	                cardiologists at a particular cancer center.

Following treatment, survivors           	              should have a yearly checkup to identify any long-term           	              consequences of cancer therapy. Those at higher risk           	              for heart complications may need more frequent monitoring.

An early and often missed warning sign of           	                heart damage, says Dr. Ewer, is a pulse rate that           	                goes up and stays up after minor exertion, such as           	                climbing stairs. “By the time patients are short           	                of breath, there may be more serious cardiac effects,” he           	                says.

If heart problems occur, stopping           	              the drug may reverse the effect. Treating the heart           	              problem can also help the heart to heal. The previously           	              mentioned 

 study found           	                that most of the metastatic breast cancer patients           	                who suffered some degree of heart damage while taking           	                Herceptin saw an improvement in heart function after           	                stopping the drug and receiving cardiac treatments,           	                such as beta-blockers and ACE inhibitors. These patients           	              were then able to resume Herceptin therapy.

In Adriana Jenkins’ case, after being           	                pulled from the Herceptin trial, she was eventually           	                able to go back on the drug after having a mastectomy. “I           	                was devastated when I was pulled from the trial,” she           	                says. But now, almost six years later, her heart is healthy and she’s cancer-free.

Editor's note: Adriana Jenkins died on Feb. 10, 2011, after a recurrence of breast cancer. 

Articles

Protecting the heart from toxic side effects of cancer therapy. 

Hazardous to Your Heart

With               certain therapies, the risk of heart damage increases throughout               a cancer survivor’s lifetime, which is why childhood cancer               survivors often experience more treatment-related effects to the               heart than adult survivors. More than 75 percent of children now               survive cancer, and the long-term effects of treatment on this             population are gaining attention. 

Children’s hearts are particularly               susceptible to certain types of chemotherapy, especially anthracyclines,               such as Adriamycin. These drugs have been used to treat childhood               cancer for more than 30 years, and although they have shown great               success in treating some cancers, such as acute leukemia, they               can also damage the heart. More importantly, the damage may get               worse over time, according to a 2006 study in the Annals of Oncology               that found heart problems can appear years and even decades after               treatment with  anthracyclines.

Radiation to the chest can also harm young hearts,               depending on the dose used and the amount of heart tissue exposed               to radiation. Radiation may damage the heart muscle, valves or               pericardium, though newer radiation methods to limit exposure have               reduced these risks.

Risk factors that increase the likelihood of heart               damage in a childhood cancer survivor include:

 The younger                 the child at the time of treatment, the greater the risk for                 heart problems.

 Girls are more susceptible to heart damage                 than boys.

 As young patients age, other risk factors for heart                 disease—such as high                 blood pressure, high cholesterol, obesity, smoking or diabetes&mdash;may increase                 the risk of treatment-related heart problems.

 Women                 who survive childhood cancer may be at risk for heart problems                 during pregnancy because increased blood volume, heart rate and                 blood pressure put extra strain on the heart.

                Some forms of exercise, such as weight-lifting, can put excessive                 strain on the heart. Adult cancer survivors should discuss any                 exercise plans with their physician.

Long-term data from the Childhood Cancer Survivor                 Study found that while less than 2 percent of children treated                 for cancer will develop severe heart problems, there is currently                 no way to predict who will be affected. However, researchers                 are making progress in identifying specific gene variations that                 put a child at higher risk for heart damage.

It’s important for childhood cancer survivors to get                 regular checkups throughout their lifetime to monitor heart health.                 Patients (or their parents) should also keep a summary of diagnosis                 and treatment, including drugs taken and test results.

Statistics on the long-term heart effects of therapy include risk factors that increase the likelihood of heart damage in a childhood cancer survivor.

Jamie Spencer

Hazardous to Your Heart

Heart Health for Childhood Cancer Patients

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