5fluoro2deoxyuridine5monophosphate

5-fluoro-2'-deoxyuridine, commonly known as floxuridine or 5-FdUrd, is a halogenated pyrimidine nucleoside analog used in cancer chemotherapy. It is the deoxyribonucleoside form of uracil with a fluorine atom at the 5-position, and it is structurally related to thymidine.

Mechanism of action

After cellular uptake, floxuridine is phosphorylated to active nucleotide species, including 5-fluoro-2'-deoxyuridine monophosphate (FdUMP). FdUMP inhibits thymidylate synthase, reducing the production of deoxythymidine monophosphate and deoxythymidine triphosphate, which impairs DNA synthesis and repair. Some metabolites may also be incorporated into nucleic acids, contributing to cytotoxic effects.

Clinical use

Floxuridine has been used primarily for treating metastases to the liver, delivered via hepatic artery infusion to achieve high local drug concentrations while limiting systemic exposure. This route exploits the liver’s first-pass extraction to maximize tumor exposure. Over time, its use has diminished with the broad adoption of other fluoropyrimidine-based regimens, though it may still appear in specialized hepatic-directed therapies.

Pharmacology and safety

Floxuridine is rapidly metabolized to active metabolites, and it has a relatively short systemic half-life. Common adverse effects include myelosuppression, mucositis, diarrhea, and liver-related toxicity, with heightened risk during hepatic artery infusion. Dosing and administration depend on the regimen and route, and monitoring is required to manage toxicity.