5Fluoruracil

5-Fluorouracil, commonly abbreviated 5-FU, is a pyrimidine analog antineoplastic agent used in chemotherapy. It is a fluorinated analog of uracil that is activated intracellularly to metabolites that interfere with nucleic acid synthesis. Its major active forms are 5-fluorodeoxyuridylate (FdUMP), which inhibits thymidylate synthase, and 5-fluorouridine triphosphate (FUTP), which is incorporated into RNA and disrupts RNA processing.

Clinical use includes colorectal cancer, pancreatic adenocarcinoma, gastric and gastroesophageal junction cancers, and head and neck cancers. It is commonly given in combination regimens such as FOLFIRI, FOLFOX, and CAPOX, and can be delivered as a continuous infusion or as a bolus injection. Leucovorin is often co-administered to enhance the effect by stabilizing the FdUMP–thymidylate synthase complex.

Capecitabine is an oral prodrug that is converted to 5-FU in tumors; thus, oral 5-FU is also used in some regimens but intravenous administration remains standard in many settings.

Metabolism is primarily by dihydropyrimidine dehydrogenase (DPD); individuals with DPD deficiency are at risk for severe toxicity. The drug is largely renally excreted. Adverse effects include myelosuppression, mucositis, diarrhea, palmar-plantar erythrodysesthesia (hand-foot syndrome), and alopecia. Toxicity can be influenced by concurrent radiotherapy or other chemotherapeutics.

Topical 5-fluorouracil formulations are used to treat actinic keratoses and some superficial skin cancers. The drug’s use and toxicity require monitoring, particularly in patients with suspected DPD deficiency or those receiving interacting treatments.