API

Mechanism of Action

Enzymes convert capecitabine to 5-fluorouracil (5-FU) in vivo. Both normal and tumor cells metabolize 5-FU to 5-fluoro-2’-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2’-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

Indication

XELODA (capecitabine) is a nucleoside metabolic inhibitor with antineoplastic activity indicated for:

• Adjuvant Colon Cancer
• Patients with Dukes’ C colon cancer
• Metastatic Colorectal Cancer
• First-line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred
• Metastatic Breast Cancer
• In combination with docetaxel after failure of prior anthracycline-containing therapy
• As monotherapy in patients resistant to both paclitaxel and anthracycline containing regimen