Protecting the Hearts of Pediatric Cancer Survivors: Dexrazoxane Before Chemo Shown to Significantly Reduce Risk of Heart Problems as Adults

Findings from a recent study revealed that a drug called dexrazoxane (Zinecard) might hinder this dreadful long-term side effect. The study published in the Journal of Clinical Oncology shows that giving dexrazoxane (commonly sold under the brand names Totect, or Zinecard) before each dose of doxorubicin substantially decreases the risk that childhood cancer survivors will have treatment-related heart problems in adulthood. That can include heart failure, a condition in which the heart doesn’t pump blood as well as it should.

SurvivorNet discussed this topic with Dr. Gabriel A. Robbins, pediatric oncologist and the medical director for the Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders at Hassenfeld Children's Hospital at NYU Langone.

“The question that this study tries to answer is an important one. We know that some of the chemotherapy agents we use to treat childhood cancers can potentially have serious side effects over the course of a lifetime. Minimizing these long-term side effects is obviously crucial for pediatric and young adult patients, since they are expected to live long lives we want them to be healthy well after they are treated for cancer,” says Dr. Robbins.

What Is Heart Failure?

Heart failure refers to a condition that affects the heart's ability to do its job (pump blood). Because the heart is struggling to meet the body's needs, fluid backs up in the body, and organs do not get as much blood as they need. It doesn't actually mean the heart is "failing" to work, but that it is not functioning as well as it could be.

To understand heart failure, it's important to understand how the heart works. Your heart is roughly the size of a fist and sits in the middle of your chest, slightly to the left. It's the muscle at the center of your circulation system, pumping blood around your body as your heart beats. This blood sends oxygen and nutrients to all parts of your body, and carries away unwanted carbon dioxide and waste products.

Chronic heart failure can impact the kidneys, liver, and lungs when it exists for a prolonged period of time, typically, more than six months.

WATCH: Tips for Living With Heart Failure

Dexrazoxane to Protect a Child’s Heart

The study evaluated the cardiovascular health of 195 people who had been diagnosed with cancer in childhood, about half of whom had received dexrazoxane prior to doxorubicin in clinical trials years earlier. This long-term research started in the 1990s.

“Answering questions about certain long-term side effects can be hard, because naturally – they take a long time to develop. So in order to study whether a new way of preventing side effects works, it requires following these patients for many years in this case, decades,” Dr. Robbins explained.

“That's part of why this study is so compelling: not only does it add to the growing evidence that dexrazoxane works well at reducing cardiac side effects of certain chemotherapies, but this study shows that the benefit seems to last at least as long as these study participants have been followed – decades. Hopefully, these patients, who are now adults, can continue to be followed, to learn if these benefits continue for their entire lives.”

The researchers pooled data from four randomized clinical trials including children with acute lymphoblastic leukemia or Hodgkin lymphoma treated with doxorubicin with or without dexrazoxane, and one trial of children with osteosarcoma (bone cancer) who received doxorubicin with dexrazoxane. Researchers prospectively assessed cardiac function among survivors from all five trials.

Median follow-up was 18.1 years and results showed an association of dexrazoxane use with superior heart function. Researchers additionally observed an association between dexrazoxane and decreased risk for lower left ventricular function (The left ventricle is one of four chambers of the heart. It’s the thickest of the heart's chambers and is responsible for pumping oxygenated blood to tissues all over the body.).

“This study makes a persuasive case that dexrazoxane is helpful in decreasing the risk of heart disease in patients that will be getting high total doses of doxorubicin and similar medications over the course of their treatment,” Dr. Robbins said.

“But there is still more to learn and study about dexrazoxane. As the study itself notes, it will be important to follow patients like this for even longer, to learn if the protective effects of dexrazoxane persist through middle adulthood and beyond. My hope is that these benefits will continue to be seen as these patients are further followed for many years in the future. But there is already enough evidence to support using dexrazoxane, and it should be an important consideration for patients who get this type of chemotherapy.”

Which children will benefit the most?

According to Dr Robbins, the children and young adults that have cancers that are treated with high total doses of doxorubicin (and similar medicines) can benefit the most. This includes people who have osteosarcoma, and certain types of leukemia and lymphoma. The patients who receive the highest total doses of this chemotherapy have been shown to have the highest risk for developing heart disease. So for children and adolescents who receive very high doses of anthracyclines, dexrazoxane may be especially helpful.

What Is Dexrazoxane?

Dexrazoxane is an injection that is used to prevent or decrease the thickening of the heart walls, which can occur after the heart is damaged. When heart muscle dies, it does not regrow back as muscle, but as scar tissue. Too much scar tissue can lead to heart failure.

Dexrazoxane injection comes as a powder to be mixed with liquid and injected into a vein by a doctor or nurse in a hospital. When dexrazoxane injection is used to prevent heart damage caused by doxorubicin, it is given over 15 minutes just before each dose of doxorubicin. When dexrazoxane injection is used to prevent tissue damage after an anthracycline medication has leaked out of a vein, it is given over 1 to 2 hours once a day for 3 days. The first dose is given as soon as possible within the first 6 hours after the leak occurs, and the second and third doses are given about 24 and 48 hours after the first dose.

Dexrazoxane indications

There is no widespread agreement on which patients receiving anthracyclines for cancer treatment are appropriate to initiate dexrazoxane. For most adults with advanced cancer who are anticipated to exceed a cumulative dose beyond 300 mg/m2 of doxorubicin (or 600 mg/m2 epirubicin).

Should all children undergoing chemotherapy receive Dexrazoxane?

Dr Robbins adds that most types of chemotherapy are not known to increase the risk of heart disease, so many patients will never need dexrazoxane. But for patients who receive doxorubicin or other similar medications in high total doses, dexrazoxane can be protective. As the study shows, this protective effect is most important for patients who receive the highest total doses of this type of chemotherapy.

Dexrazoxane Side Effects

Side effects of this medication may include:

• Alopecia
• Nausea/Vomiting
• Fatigue
• Anorexia/ Loss of appetite
• Stomatitis
• Fever
• Diarrehea
• Pain or swelling in the place where the medication was injected

Are There Other Options to Prevent Heart Failure After chemotherapy?

“New medications are currently being studied that could one day replace anthracyclines and still be as effective at treating cancer, without having the same risk for long-term side effects like heart disease,” Dr. Robbins said. “Doctors are also studying newer versions of anthracyclines that are made in such a way that they might not be able to penetrate the heart muscles as easily, thereby preventing damage. But for now, while anthracyclines are still an important part of effective treatment, dexrazoxane appears to be the best way to help protect our patients' hearts.”

Adopting Healthy Habits to Manage Heart Failure

According to the American Heart Association, following recommendations about diet, exercise, and other habits can help alleviate heart failure symptoms, slow your disease's progression, and improve your everyday life. In fact, people with mild to moderate heart failure often can lead nearly normal lives as a result. Making some of these lifestyle changes can be easier said than done. But working these changes into your daily routine can make a real difference in your quality of life.

Is It Possible My Child Could Have Late Effects of Cancer Treatment?

Each child getting cancer treatment is unique. Therapies used vary from child to child and from one type of cancer to another. Other things that can affect a child's risk include:

• The type of cancer
• Where the cancer is in the body
• Child’s age
• Child's overall health before the cancer
• Child's genetic make-up (inherited risk for certain health problems)

Late effects are caused by the damage that cancer treatment does to healthy cells in the body. Most late effects are caused by chemotherapy or radiation. Major surgery can also lead to late effects.

WATCH: What to Expect From Your Child’s Lymphoma Treatment

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