5Fluorouracil

5-fluorouracil (5-FU) is a fluorinated pyrimidine antimetabolite used in cancer chemotherapy. It primarily inhibits thymidylate synthase after conversion to active metabolites, reducing deoxythymidine monophosphate (dTMP) and impairing DNA synthesis. In addition, some metabolites are incorporated into RNA, disrupting RNA processing and function. These actions slow or halt the proliferation of rapidly dividing cells.

Clinical use varies by regimen and tumor type. 5-FU is a backbone of colorectal cancer chemotherapy, often given with leucovorin and other agents in regimens such as FOLFOX or CAPOX. It is also used in head and neck cancers, pancreatic cancer, and certain GI malignancies. Topical 5-FU formulations are used to treat actinic keratoses, superficial basal cell carcinoma, and other precancerous or early skin lesions.

Administration and pharmacology. 5-FU is commonly given by intravenous infusion, either as a bolus or longer infusion. Capecitabine is an oral prodrug that is converted to 5-FU in tumor tissue. The drug is metabolized by the liver and excreted by the kidney; deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD) can cause severe toxicity due to impaired catabolism. Leucovorin can enhance the effectiveness of 5-FU but also increases toxicity.

Common adverse effects include myelosuppression, mucositis, diarrhea, nausea, vomiting, and hand-foot syndrome (especially with prolonged infusions or capecitabine). Other risks include dermatitis, alopecia, and, less frequently, hepatotoxicity or cardiotoxicity. Dose adjustments and toxicity monitoring are important, particularly in patients with renal or hepatic impairment or DPD deficiency.