Cardio-Oncology: Fluoropyrimidine Chemotherapy

Treatment using drugs to kill cancer cells is called chemotherapy. More than 100 chemotherapy drugs are used in cancer treatments.

If you have cancer, your treatment will depend on the type of cancer you have and how far it has progressed. While your treatment will target the cancer cells, sometimes it also may cause heart problems. Although these heart side effects are rare, it’s important to understand and be aware of them.

Chemotherapy with fluoropyrimidine, which includes 5-fluorouracil (5FU) and capecitabine, may be used to treat solid tumors such as those involving your stomach and intestine (gastrointestinal), breast, or head and neck.

These medicines belong to a type of chemotherapy called antineoplastic or antimetabolite, which describes how they work on cancer cells. The drugs stop cancer cells from forming DNA — which contains genetic information — and growing.

This chemotherapy is often well tolerated, but you can have side effects depending on other medications you are taking. Your health history including age, risk factors for heart disease, and other chemotherapy treatments can also play a role in whether you develop complications.

The most common side effects with this chemotherapy are fatigue, nausea, diarrhea and lab abnormalities. It also can cause heart side effects including chest pain, spasm of the heart arteries or irregular heart rhythms, which can be felt as palpitations.

Use this condition center to learn more about damage to your heart, also called cardiotoxicity, from chemotherapy using 5-fluorouracil or capecitabine.

Cancer Types Treated

Many cancer types are treated with chemotherapy using fluoropyrimidine including:

• Gastrointestinal cancers, including colorectal cancer, anal cancer, some stomach cancers
• Breast cancer
• Lung cancer
• Esophageal cancer
• Head and neck cancer

Other cancers also receive this treatment:

• Hepatobiliary cancers (liver or gallbladder)
• Ovarian, fallopian tube, or peritoneal cancers
• Neuroendocrine (islet cell tumors)
• Pancreatic cancer

Chemotherapy may be given through a tube placed in a vein as an intravenous (IV) medication or with a pill taken by mouth. The IV form, 5-flourouracil, is given either continuously over hours or as one dose over minutes. The pill, capecitabine, may be taken twice a day.

Heart Conditions Linked

Although rare, some people may have side effects linked to 5FU or capecitabine chemotherapies that affect their hearts. Up to 6 people out of 100 patients receiving this treatment have cardiac side effects.

While some people have no symptoms, others might feel a chest pressure or pain. If you feel this or other side effects, your doctor may do an electrocardiogram (ECG) that measures the electrical activity of your heart. The test can detect a possible heart attack.

Why Does Chemotherapy Cause Chest Pain?

Chest pain may happen because 5FU can affect the coronary arteries. These arteries sometimes spasm (coronary vasospasm) causing blood flow to decrease. When that happens, your heart muscle may not get enough oxygen and nutrients to function well.

If you feel chest pain after having chemotherapy, call 911 and seek emergency care.

Chest Pain (Angina)

The most common heart symptom due to 5FU chemotherapy is chest pain or pressure that lasts a short time and feels like you are having a heart attack. You may feel like your chest is being squeezed, or have a feeling of heaviness, pressure, weight, or tightness in your chest. You also may feel a burning in your chest. The pain can radiate to the shoulder, neck, jaw, arm or back. The chest pain may lessen when the chemotherapy is stopped. If you experience chest pain, call 911 or go to the emergency room.

Irregular Heart Rhythms (Arrhythmias)

Normal heart function relies on a series of electrical events inside the heart that occur at the right time and in the right order. Chemotherapy with 5FU can damage the heart’s electrical system and disturb your heart rhythm. An irregular heart rhythm is called an arrhythmia. An arrhythmia can mean your heart rhythm is too fast or too slow. Your cancer doctor or treatment team may monitor your heart rhythm with an ECG.

Some patients may have palpitations — your heart beating rapidly and loudly in your chest — irregular heartbeat, skipped beats or other uncomfortable chest sensations. If you have these symptoms, feel lightheaded or dizzy, or if you faint while getting your chemotherapy, seek medical attention at once.

Heart Failure 

Other less common complications from 5FU chemotherapy can include damage to the heart muscle causing the heart to weaken and not be able to pump blood well. This is known as a cardiomyopathy or heart failure and can result in fluid building up in your body causing:

• Swelling in the feet or legs
• Stomach or abdominal distension
• Difficulty breathing with exertion (such as going up a flight of stairs)
• Inability to lie flat on your back
• Waking up in the middle of the night feeling short of breath
• Sudden weight gain

If you experience any of these symptoms, talk to your doctor.

When Do Heart Side Effects Occur?

The timing of chest pain symptoms from 5FU chemotherapy depends on the type of chemotherapy (if it is given as an IV or as a pill) and how it is given (in one dose or continuous infusion).

More: Learn about Angina

IV infusion (5FU): When given in one dose (as a bolus), chest pain can occur during the infusion or a few hours afterward.

The continuous IV infusion is given over two to four days with a pump that you may take home. When given this way, the chemotherapy may reach certain parts of the body more slowly. Symptoms can occur between 12-72 hours after starting the infusion. With more cycles of continuous infusions, symptoms may begin earlier in the cycle, become more intense, and last longer.

Oral pill (capecitabine): The pill version, capecitabine, is processed by the body more slowly. As a result, the symptoms are like those experienced with continuous infusion. Side effects may be less intense and start 12-72 hours after starting the medicine.

How Will I Know If I Have Cardiotoxicity?

People who get heart symptoms or other problems from 5FU chemotherapy usually feel the side effects during the first or second cycles of treatment. Most people go through these chemotherapy regimens without heart complications.

If you don’t have symptoms during your first or second cycles, then it is unlikely you will have heart side effects later.

What Increases Your Risk of Cardiotoxicity?

5FU Risks

The way you receive the medicine can increase your likelihood of developing heart symptoms.

• If you receive the intravenous form, you are more likely to develop symptoms than if you take the pill by mouth.
• If you receive the continuous infusion of the chemotherapy, you may be more likely to develop symptoms than if given the infusion in one dose.
• If you receive the infusion in one dose, you may feel more intense symptoms sooner compared with continuous infusion or the oral pill.

Other Risk Factors 

Your personal risk factors may increase your likelihood of developing heart problems from 5FU chemotherapy.

History of Heart Disease: If you have coronary artery disease or blockages in your heart, you have a higher likelihood of developing cardiac symptoms from 5FU chemotherapy. They can even be life-threatening. Talk to your cancer doctor and your cardiologist (heart doctor) about the potential heart side effects of these medications.

A history of coronary artery disease does not mean that you can’t be treated with the 5FU chemotherapy. It is important that all heart risk factors — including your blood pressure and cholesterol — are addressed before chemotherapy begins.

Heart Disease Risk Factors: If you don’t have coronary artery disease, other factors may increase your chance of developing cardiac complications. It is important to talk with your care team about what increases your risk including whether you have:

• Diabetes (type 1 or type 2)
• High blood pressure
• High cholesterol
• Obesity
• Family history of heart disease

If you smoke or use nicotine, it’s important to stop. Nicotine and tobacco can increase your risk of developing spasm of the heart arteries (coronary vasospasm).

When to Call a Doctor

If you have chest pain with the 5FU chemotherapy, you should stop the drug at once and seek medical care. If you are in the hospital or a chemotherapy suite, tell your care team right away. If you are at home, go to the nearest emergency room.

As always, if you are having severe chest pain at any time, call 112, seek and emergency care.

It also is important to seek medical attention if you experience palpitations, lightheadedness, dizziness, or feel like you are going to faint.

During chemotherapy, you will see your cancer doctor, oncology nurses, and other health professionals often. Be sure to talk to them about any symptoms you notice.

Exams and Tests

What types of heart tests might I need before starting cancer treatment?

You likely will get a baseline ECG before starting chemotherapy. Be sure to talk with your oncologist or cardiologist about your heart history. You also will discuss what other tests, if any, are needed.

What types of heart tests might I have to detect fluoropyrimidine cardiotoxicity?

If you have chest pain, you may get tests to check for heart muscle damage. Knowing when the symptoms started and what type of chest pain you are feeling will be important. Tests you may have:

• Lab tests (blood work) to look for heart muscle damage
• ECG
• Ultrasound of the heart called an echocardiogram
• Chest X-ray
• Computed tomography (CT) scan or the coronary arteries (coronary CT angiogram)
• Stress testing
• Cardiac catheterization

These tests help assess the overall health of your heart arteries. You may need more testing or procedures if the tests show that you have blockages in your heart because of pre-existing coronary artery disease or your cardiac risk factors. To learn more, go to What Increases Your Risk.

Prevention

What steps can I take to help reduce my risk of developing cardiotoxicity?

There is no way to know for sure who might develop heart problems from 5FU chemotherapy. However, people who already have heart risk factors or coronary artery disease — or both — have a higher likelihood of cardiotoxicity. During cancer treatment and for your overall health, it’s a good idea to follow heart-healthy behaviors.

Blood Pressure

Blood pressure control is important during your cancer treatment and for your overall health. Your goal for blood pressure depends on your age and other health problems. Your blood pressure will be checked at every visit during your treatment.

If you are concerned that your blood pressure is too high or too low, you may want to check your blood pressure at home and bring those readings to your health visits.

The medications to treat 5FU or capecitabine cardiotoxicity are also ones that can affect your blood pressure. These medications (anti-anginals) work to stop coronary vasospasm. If you have chest pain, your doctor may give you one or more of these medications.