Medical

Focus on: Chemotherapy and the heart

Illustration representing the NADPH oxidase enzyme and the heart

Chemotherapy is a vital treatment for cancer, but in high doses it can damage the heart. Dr David Grieve, Senior Lecturer in Cardiovascular Physiology at Queen’s University, Belfast, tells Judy O’Sullivan about his research to discover why this happens and how it could be prevented.

Ask anyone to name a cancer treatment and the answer will almost certainly be chemotherapy. First used to combat cancer back in the 40s, it acts by killing cancer cells, preventing the tumour from growing. There are around 50 different chemotherapy agents, which can be given as an injection, an infusion (drip) into a vein or simply as a tablet.

Chemotherapy can be used either to cure cancer, to relieve its symptoms or to reduce the risk of cancer re-occurring, and it is often used in combination with other treatments such as radiotherapy.

Why research is needed

It’s well known that chemotherapy is highly effective in destroying tumours and reducing the risk of cancer spreading. However, high doses can cause heart failure – which means that the heart muscle is no longer as efficient as it should be at pumping blood around the body.

Heart failure can be both debilitating and life-threatening, so it’s vital that cancer patients don’t develop it as a side effect of their treatment. And of course, some people with cancer have heart disease to begin with, so they are at higher risk of heart failure in the first place.

"Heart failure can be both debilitating and life-threatening, so it’s vital that cancer patients don’t develop it as a side effect of their treatment"

To avoid causing the condition, cancer specialists (oncologists) often have to prescribe low doses of chemotherapy, which unfortunately aren’t as effective at destroying cancer cells.

Our research is focusing on understanding exactly how high-dose chemotherapy can cause heart failure so we can either prevent this happening or more accurately identify cancer patients who are at increased risk.

Ultimately, we hope our research will enable people with cancer to safely receive the levels of chemotherapy that they need to be treated successfully.

Results so far

Our research involves examining the effects of high levels of doxorubicin, the most commonly used type of chemotherapy, but our findings are also relevant to other types. We know that at the current maximum dosing limit – which only a small number of patients receive – seven in every 100 people who are given doxorubicin will develop heart failure.

So far our research has established that an enzyme called NADPH oxidase, which occurs naturally in the body but is increased in disease, plays an important role in causing heart failure in response to chemotherapy. When we gave high doses of doxorubicin chemotherapy to mice and blocked the activity of this enzyme, we discovered that they were protected against heart failure.

We’re now trying to understand exactly how this enzyme causes heart failure in response to chemotherapy and whether blocking its action in cancer patients could prevent this from happening. As NADPH oxidase occurs naturally in the body, it’s likely that it has an important function, although high levels found in people with chronic disease may indicate that it has a damaging role in this situation.

So we need to understand exactly how this enzyme works before we can start thinking about blocking its actions in patients. Added to this, we need an easier way of measuring NADPH oxidase levels in the heart, which could be important for identifying and monitoring heart failure in chemotherapy patients. At the moment, the only way is by taking a sample of heart tissue, which isn’t practical.

Looking to the future

"Although our findings are encouraging, it’s likely to take up to ten years before cancer patients will benefit from our work"

Our research could eventually save lives in two ways. First, if we could safely give a drug to block the action of the NADPH oxidase enzyme in cancer patients, high-dose chemotherapy could be given without causing heart failure.

Second, if we could easily measure levels of NADPH oxidase in the heart, then we may be able to identify a cancer patient’s risk of developing heart failure in response to a particular chemotherapy agent and adjust their treatment accordingly.

Although our findings are encouraging, it’s likely to take up to ten years before cancer patients will benefit from our work. In the meantime, we’re very grateful to the BHF for funding this stage of our research as we simply wouldn’t be able to do it without its continued support.

Worried about chemo?

For most people, the benefits of chemotherapy will outweigh the risks. The side effect of heart failure is rare and is only associated with high doses, so those levels aren’t often given.

Before you have chemotherapy, your cancer specialist should discuss the risks and benefits for you as an individual. However, if you or a loved one has any questions or concerns about treatments for cancer, call the free Macmillan Cancer Support line at 0808 808 00 00 or visit macmillan.org.uk

Find out more

Macmillan booklet - Heart health and cancer treatmentFor more information, order the new booklet called Heart Health and Cancer Treatment jointly produced by Macmillan Cancer Support and the British Heart Foundation. It’s written for people who are having cancer treatment, whether you’ve been told that your treatment may affect your heart or if you already have a heart condition and need to have treatment for cancer.

You may also find the booklet useful if you would like to know more about how to improve the health of your heart before, during and after cancer treatment.

Order free copies from Macmillan Cancer Support at be.macmillan.org.uk

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