Diagnosed with Cancer? Your two greatest challenges are understanding cancer and understanding possible side effects from chemo and radiation. Knowledge is Power!
Learn about conventional, complementary, and integrative therapies.
Dealing with treatment side effects? Learn about evidence-based therapies to alleviate your symptoms.
Click the orange button to the right to learn more.
- You are here:
- Home »
- Blog »
- side effects ID and prevention »
- 5-fluorouracil (5-FU) Heart Damage
5-fluorouracil (5-FU) Heart Damage
5-fluorourcil (5-FU) capecitabine kills cancer cells. The problem is this chemotherapy regimen is cardiotoxic which means that it can cause heart damage. The cancer patient’s choice is to either not undergo 5-fluorouracil (5-FU) capecitabine or undergo 5-fluorourcil and risk heart damage.
A third option would be to undergo therapies shown to minimize your risk of heart damage.
There was no discussion of this side effect and certainly no discussion of therapies to reduce the risk of developing heart damage.
I don’t agree with the article below when it says that cardiotoxicity usually exhibits problems within the first 24 hours. My chemotherapy-induced cardiomyopathy and Atrial Fibrillation happened fully 15 years AFTER my cardiotoxic chemo regimens.
What are the pros and cons of 5-fluorouracil?
Pros:
- Effectiveness: 5-FU is effective in treating a range of cancers, particularly colorectal cancer, and is often used as a first-line treatment or in combination with other medications.
- Versatility: It can be administered in different ways, including intravenously, topically (for skin cancer), or as part of a chemotherapy regimen.
- Adjuvant Therapy: 5-FU is often used as adjuvant therapy after surgery to help prevent cancer recurrence.
- Well-Established: It has been in use for many years and its efficacy and side effects are well-documented, allowing for better management and prediction of outcomes.
Cons:
- Side Effects: Common side effects of 5-FU include nausea, vomiting, diarrhea, and mucositis. These side effects can be severe and impact a patient’s quality of life during treatment.
- Toxicity: 5-FU can cause significant toxicity, particularly to the bone marrow, leading to decreased production of blood cells and anemia.
- Risk of Hand-Foot Syndrome: Some patients may develop hand-foot syndrome, a condition characterized by redness, swelling, and pain on the palms of the hands and soles of the feet.
- Resistance: Some cancers may develop resistance to 5-FU over time, leading to decreased effectiveness of the medication.
- Long-Term Effects: There is a risk of long-term side effects, including damage to the heart, liver, and kidneys, although these are less common.
- Skin Sensitivity: For topical application, 5-FU can cause skin irritation, redness, and sensitivity to sunlight.
What therapies may reduce the risk of 5-fluorourcil (5-FU) capecitabine causing heart damage?
man hand holding his nutritional supplemets, healthy lifestyle background.
- Daily moderate exercise
- Heart healthy nutrition
- CoQ10
- Omega-3 fatty acids
- Curcumin
David Emerson
- Cancer Survivor
- Cancer Coach
- Director PeopleBeatingCancer
Fluoropyrimidine Cardiotoxicity
“The fluoropyrimidines, namely 5-fluorouracil (5-FU) capecitabine, are the third most commonly used chemotherapeutic class for the treatment of solid tumors of glandular and squamous origin, such as
- head and neck,
- esophageal,
- stomach,
- and bladder.
Use of fluoropyrimidines is standard of care for treatment of advanced colorectal cancers and may have synergetic effects with external-beam radiation to enhance the radiosensitivity of tumors.1
However, among conventional cytotoxic chemotherapies, 5-FU is likely one of the most common chemotherapeutic agents to cause cardiotoxicity, second only to anthracyclines.
Reported clinical manifestations have largely been consistent with angina attributed to coronary vasospasm, although myocardial infarction,
- heart failure,
- arrhythmias,
- pericarditis,
- coronary dissection,
- QT prolongation, and
- sudden cardiac death
have also been reported in the setting of fluoropyrimidine use…2
These agents therefore function as S-phase antimetabolites and promote genomic instability by inducing double-strand DNA and single-strand DNA breaks, as well as by interfering with DNA synthesis, repair, and elongation…3
Coronary vasospasm remains the most well-established manifestation of fluoropyrimidine cardiotoxicity, as supported by in vitro models of concentration-dependent vasoconstriction by 5-FU on vascular smooth muscle cells.5 However, some patients with reduced ejection fraction by echocardiography have been reported to demonstrate left ventricular wall motion abnormalities in areas that do not correspond to a classic coronary vessel distribution, suggesting that the mechanisms of cardiotoxicity may be multifactorial.6
Direct toxicity to the myocardium has been proposed to be mediated by cardiotoxic metabolites such as fluoroacetate and fluorocitrate.7 Direct toxicity to the coronary endothelial intima may contribute to thrombosis.8 In vivo studies in rabbits have demonstrated apoptosis of epicardial cardiomyocytes and endothelial cells of the distal coronary arteries as a consequence of 5-FU treatment, leading to inflammation as seen in myocarditis.9
An in vitro study demonstrated increased reactive oxygen species in cardiomyocytes and endothelial cells in the setting of 5-FU exposure.10 Takotsubo cardiomyopathy has been described in case reports and is thought to be secondary to an exaggerated sympathetic response.11 Other suggested mechanisms include transformation of erythrocyte membranes to echinocytic shapes, leading to increased blood viscosity, reduced oxygen carrying capacity, and subsequent ischemia,12 as well as vasospasm mediated by an allergic reaction arising from 5-FU exposure (Kounis syndrome).13
Although fluoropyrimidine-associated cardiotoxicity was first observed as early as the 1960s, there have been few clinical trials focused specifically on defining the incidence of cardiotoxicity, which is thought to range from 1% to 19%.14 In general, reported incidence data have been based largely on retrospective studies that lack consistent definitions of cardiotoxicity and have variable reporting of cardiac events…
More recently, an analysis of 16 clinical trials incorporating 5-FU and capecitabine treatment in the ECOG-ACRIN Cancer Research Group database found that most trials excluded patients with known preceding cardiovascular disease.15 The remaining studies did not account for pre-existing cardiovascular disease. Overall, less than half of the trials reported adverse cardiac events potentially related to 5-FU administration, highlighting the need for more robust studies to assess the incidence and mechanisms associated with fluoropyrimidine cardiotoxicity.
Proposed risk factors for fluoropyrimidine cardiotoxicity include older age, concurrent administration of other cardiotoxic medications, and a preceding history of cardiac disease and cardiovascular risk factors. Continuous infusions have been associated with a higher incidence of cardiotoxicity as opposed to bolus dosing.16
Cardiotoxicity most commonly occurs during the first cycle of 5-FU administration, with a mean time to symptoms around 12 hours.17 Diagnosis is typically based on the presence of symptoms such as chest pain, electrocardiographic changes, elevated cardiac biomarkers, and changes in left ventricular function by echocardiography and/or the results of coronary angiography…
High-risk patients presenting with 5-FU-associated angina should undergo emergent coronary angiography with revascularization as needed, and lower-risk patients with anginal symptoms should undergo exercise stress testing or coronary computed tomography angiography after symptom resolution.
In addition to the use of commonly accepted cardiovascular medications, uridine triacetate was approved by the U.S. Food and Drug Administration in 2015 as an antidote for fluoropyrimidine toxicity. Uridine triacetate is the oral prodrug of uridine, a natural pyrimidine nucleoside that competes with 5-fluorouridine-5′-triphosphate incorporation into RNA, therefore attenuating fluoropyrimidine toxicity in normal tissue…
In summary, fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is limited by cardiotoxicity in 1-19% of patients. The exact incidence and mechanisms of cardiotoxicity have yet to be elucidated. A diverse range of clinical presentations have been reported, including the development of angina mediated by coronary vasospasm, myocardial infarction, acute cardiomyopathy, and arrhythmias.