Fluorouracil

Fluorouracil, commonly known as 5-fluorouracil (5-FU), is a chemotherapy agent and antimetabolite used to treat various cancers. It is a pyrimidine analog of uracil that interferes with nucleotide synthesis. After cellular uptake, 5-FU is converted into several active metabolites, including FdUMP, FUTP, and FdUTP, which disrupt DNA and RNA synthesis and function.

The principal mechanism is inhibition of thymidylate synthase by FdUMP, lowering intracellular dTMP and DNA synthesis. FUTP and FdUTP can be incorporated into RNA and DNA, impairing RNA processing and function. Leucovorin (folinic acid) is often co-administered to enhance thymidylate synthase inhibition and therapeutic effect.

Clinical use includes systemic chemotherapy for colorectal cancer and other gastrointestinal cancers, as well as head and neck and pancreatic cancers in combination regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX. Topical 5-FU formulations are used to treat actinic keratoses and some superficial skin cancers.

5-FU is typically given by intravenous infusion or bolus injection; topical formulations are applied to the skin. The drug is primarily metabolized by dihydropyrimidine dehydrogenase (DPD); reduced or absent DPD activity can cause severe toxicity. Common adverse effects include myelosuppression, mucositis, diarrhea, nausea, and hand-foot syndrome.