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.

XELODA (capecitabine) is a nucleoside metabolic inhibitor with antineoplastic activity indicated for:
• Adjuv ant 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 anthracyclinecontaining therapy – As monotherapy in patients resistant to both paclitaxel and an anthracycline-containing regimen

• Take XELODA with water within 30 min after a meal
• Monotherapy: 1250 mg/m2 twice daily orally for 2 weeks followed by a one-week rest period in 3-week cycles
• Adjuvant treatment is recommended for a total of 6 months (8 cycles).
• In combination with docetaxel, the recommended dose of XELODA is 1250 mg/m2 twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m2 as a 1-hour IV infusion every 3 weeks.
• XELODA dosage may need to be individualized to optimize patient management.
• Reduce the dose of XELODA by 25% in patients with moderate renal impairment.

Most common adverse reactions (≥30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported.

• Severe Renal Impairment.
• Hypersensitivity.

• Coagulopathy: May result in bleeding, death. Monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly.
• Diarrhea: May be severe. Interrupt XELODA treatment immediately until diarrhea resolves or decreases to grade 1. Recommend standard antidiarrheal treatments.
• Cardiotoxicity: Common in patients with a prior history of coronary artery disease. See package insert for complete information.