From the Guidelines
5-Fluorouracil (5-FU) can cause several adverse reactions, with cardiac toxicity being a significant concern, including chest pain, arrhythmias, and rarely cardiomyopathy, especially in patients with pre-existing heart conditions, as reported in a study published in the Journal of the American College of Cardiology 1.
Adverse Reactions to 5-FU
The adverse reactions to 5-FU can be categorized into several groups, including:
- Gastrointestinal issues, such as nausea, vomiting, diarrhea, and stomatitis (mouth sores)
- Bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia, which increases infection risk
- Neurological toxicities, such as cerebellar dysfunction and peripheral neuropathy
- Cardiac toxicity, including chest pain, arrhythmias, and rarely cardiomyopathy
- Ocular toxicities, like excessive tearing and photophobia
Cardiac Toxicity
Cardiac toxicity is a significant concern with 5-FU, with a reported incidence of myocardial ischemia as high as 10% 1. The mechanisms of 5-FU-induced myocardial ischemia are multifactorial and include coronary vasospasm and endothelial injury. Chest pain and ischemic ECG changes typically occur at rest, and less frequently during exercise, within days of drug administration and sometimes persist even after treatment cessation.
Management
Management of adverse reactions to 5-FU includes dose adjustments, supportive care, and in severe cases, discontinuation of 5-FU. It is essential to monitor patients closely for signs of cardiac toxicity, including chest pain and ischemic ECG changes, and to adjust the dose or discontinue treatment as needed.
Key Points
- 5-FU can cause cardiac toxicity, including chest pain, arrhythmias, and rarely cardiomyopathy
- The incidence of myocardial ischemia can be as high as 10%
- Management includes dose adjustments, supportive care, and in severe cases, discontinuation of 5-FU
- Close monitoring of patients for signs of cardiac toxicity is essential 1
From the FDA Drug Label
The most frequent adverse reactions to fluorouracil occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration Ulcerations, other local reactions, cases of miscarriage, and a birth defect (ventricular septal defect) have been reported when fluorouracil was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect Although a causal relationship is remote, other adverse reactions which have been reported infrequently are: Central Nervous System: Emotional upset, insomnia, irritability. Gastrointestinal: Medicinal taste, stomatitis. Hematological: Eosinophilia, thrombocytopenia, toxic granulation Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash. Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation. Miscellaneous: Herpes simplex
The adverse reactions to 5-Fluorouracil (5-FU) include:
- Local reactions: burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration
- Hematological side effects: leukocytosis, eosinophilia, thrombocytopenia, toxic granulation
- Central Nervous System: emotional upset, insomnia, irritability
- Gastrointestinal: medicinal taste, stomatitis
- Integumentary: alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash
- Special Senses: conjunctival reaction, corneal reaction, lacrimation, nasal irritation
- Miscellaneous: herpes simplex 2
From the Research
Adverse Reactions to 5-Fluorouracil (5-FU)
The following are some of the adverse reactions associated with 5-Fluorouracil (5-FU):
- Neurotoxicity, which can present as symptoms similar to stroke, such as encephalopathy 3
- Cardiotoxicity, which can manifest as atypical chest pain, cardiac arrhythmia, myocardial infarction, or global cardiac failure 4, 5
- Myelosuppression, gastrointestinal complications, and neurotoxicity, which can be life-threatening 6
- Stomatitis, diarrhea, dermatitis, and myelosuppression, which are the main toxicities of 5-FU 7
- Neurologic toxicity, which can vary from mild to severe and prolonged, especially in patients with dihydropyrimidine dehydrogenase (DPD) deficiency 7
- Hand-foot syndrome, which is a well-known toxicity of 5-FU 5
- Mucositis, which can be severe and prolonged 7
- Desquamating dermatitis, which can be a severe side effect of 5-FU 7
Risk Factors for Adverse Reactions
Certain patients may be at higher risk of developing adverse reactions to 5-FU, including: