fluoropyrimidinebased

Fluoropyrimidine-based drugs are a class of anticancer agents derived from pyrimidine nucleoside analogs in which a fluorine atom substitutes for hydrogen. The most widely used agents in this class include 5-fluorouracil (5-FU) and several prodrugs such as capecitabine, tegafur, and combinations like S-1.

Their antineoplastic effects arise mainly from inhibition of thymidylate synthase, leading to depletion of dTMP and impaired DNA synthesis. Metabolites of these compounds can also be incorporated into RNA as FUTP, disrupting RNA processing and function.

5-FU is active after intracellular metabolism; capecitabine and tegafur are oral prodrugs that are converted to 5-FU in liver and tumor tissues. S-1 combines tegafur with uracil and oteracil to modulate activation and reduce gastrointestinal toxicity.

Fluoropyrimidines are used to treat colorectal cancer, gastric cancer, pancreatic cancer, and some breast and head and neck cancers, often in combination with leucovorin or radiotherapy to enhance efficacy.

Common toxicities include myelosuppression, mucositis, diarrhea, and hand-foot syndrome (especially with capecitabine). DPD deficiency can cause severe, potentially life-threatening toxicity, so pharmacogenetic testing may be considered in some settings.

First described in the late 1950s, 5-FU became a cornerstone of chemotherapy and remains a standard component of many regimens, with ongoing development of new prodrugs and combination strategies.