Fluorouracil (5-FU) is a long-standing chemotherapy medication. As an antimetabolite, it interferes with the fundamental processes of cell growth and division. For decades, 5-FU has been a key component in treating various cancers by disrupting the rapid proliferation of cancer cells.
How Fluorouracil Works and is Used
Fluorouracil disrupts the production and repair of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) within cancer cells. It acts as a “faulty building block,” specifically a pyrimidine analog, that cancer cells mistakenly incorporate into their genetic material. Once inside the cell, 5-FU is converted into active metabolites, such as fluorodeoxyuridine monophosphate (FdUMP). FdUMP then binds to and inhibits an enzyme called thymidylate synthase (TS), which is necessary for creating thymidylate, a molecule needed for DNA synthesis. This interference leads to a scarcity of DNA building blocks, causing rapidly dividing cancer cells to undergo cell death.
Fluorouracil is employed to treat a range of cancers, including those of the colorectal, breast, stomach, pancreatic, esophageal, and anal regions. It is also used for certain skin cancers like actinic keratosis and superficial basal cell carcinoma.
Fluorouracil can be administered in two primary ways: systemically or topically. For internal cancers, it is usually given intravenously (IV), either as a continuous infusion via a portable pump over several days or as a rapid injection, known as a bolus. Often, IV 5-FU is combined with another drug, leucovorin, which can enhance its effectiveness by stabilizing the binding of FdUMP to thymidylate synthase. For skin conditions, fluorouracil is applied directly to the affected area as a cream or solution.
Common Side Effects of Treatment
Systemic fluorouracil treatment can lead to various side effects. Gastrointestinal issues are frequently reported, including nausea, vomiting, and diarrhea. The drug can also cause mucositis, which manifests as painful sores and inflammation in the mouth and along the digestive tract lining. These symptoms arise because fluorouracil targets fast-growing cells, which include the healthy cells lining the digestive system.
Skin and hair changes are also common during treatment. Patients may develop hand-foot syndrome, medically known as palmar-plantar erythrodysesthesia, characterized by redness, swelling, pain, and sometimes peeling on the palms of the hands and soles of the feet. Hair thinning or loss is another possibility, though it is often temporary, with hair growth resuming after treatment. Skin may also become more sensitive to sunlight, requiring careful sun protection.
Fluorouracil can suppress bone marrow activity, a condition called myelosuppression, which impacts the production of blood cells. This can result in neutropenia, a decrease in white blood cells that heightens the risk of infection. Anemia, or low red blood cell count, can lead to fatigue, while thrombocytopenia, a reduction in platelets, increases the likelihood of bruising and bleeding. Topical fluorouracil generally causes localized side effects, such as redness, burning, crusting, and irritation at the application site.
Managing Side Effects and Monitoring
Managing side effects is an important part of fluorouracil treatment, with various strategies available to help patients. For gastrointestinal symptoms like nausea and vomiting, healthcare providers often prescribe anti-nausea medications, also known as antiemetics. Special mouthwashes can help alleviate the discomfort of mucositis or mouth sores, while dietary adjustments, such as avoiding high-fiber foods during episodes of diarrhea, can help manage bowel issues. For hand-foot syndrome, using moisturizers and avoiding pressure on the palms and soles can provide relief.
Patients are encouraged to adopt self-care practices to manage side effects. Maintaining good hydration by drinking plenty of fluids is beneficial, especially when experiencing diarrhea or vomiting. Practicing gentle oral hygiene can help prevent and manage mouth sores. Protecting skin from the sun, using sunscreen with an SPF of at least 30, and seeking shade are important due to increased sun sensitivity. Ensuring adequate rest also supports the body’s recovery during treatment.
Regular medical monitoring is essential during fluorouracil therapy. Healthcare teams closely track a patient’s progress through routine blood tests, which monitor blood cell counts and assess liver and kidney function. These tests help detect bone marrow suppression and other potential issues early. Based on the severity of any side effects, the treatment schedule or dosage of fluorouracil may be adjusted to optimize patient safety and comfort.
Serious Risks and Genetic Considerations
Fluorouracil can lead to serious side effects. These include cardiotoxicity, which can manifest as chest pain, abnormal heart rhythms, or other heart problems. Neurotoxicity is another rare but serious risk, potentially causing confusion, disorientation, balance issues, or even seizures.
Dihydropyrimidine Dehydrogenase (DPD) deficiency is a key consideration before starting fluorouracil treatment. DPD is an enzyme responsible for breaking down over 80% of the administered fluorouracil in the body. DPD deficiency is a genetic condition where individuals have reduced or absent activity of this enzyme. If a patient has DPD deficiency, the drug can accumulate to toxic levels, leading to severe or potentially life-threatening side effects, even at standard doses. These severe reactions can include profound myelosuppression, severe diarrhea, and extensive mucositis. Testing for DPD deficiency may be performed before treatment to identify at-risk individuals, allowing for dosage adjustments or the consideration of alternative therapies to enhance patient safety.