Doxifluridines

Doxifluridine, also known as 5'-deoxy-5-fluorouridine, is a nucleoside analog that serves as a prodrug of the chemotherapeutic agent 5-fluorouracil (5-FU). It is administered orally to deliver 5-FU systemically, with the aim of achieving tumor-targeted exposure.

Activation occurs primarily through thymidine phosphorylase, an enzyme commonly upregulated in solid tumors, which converts doxifluridine to 5-FU within tumor tissue. 5-FU then exerts cytotoxic effects by inhibiting thymidylate synthase and by incorporating into RNA and DNA.

Pharmacology and administration: After oral dosing, doxifluridine is absorbed and metabolized to 5-FU; its pharmacokinetics are influenced by enzyme activity and organ function. Adverse effects mirror those of 5-FU, including myelosuppression, mucositis, diarrhea, and sometimes hand-foot syndrome.

Clinical status: Doxifluridine has been evaluated in colorectal and gastric cancer, among other indications, as monotherapy and in combinations. It is not widely used today; other 5-FU prodrugs, such as capecitabine, have largely supplanted it. Research persists in select trials comparing efficacy and safety profiles.