Brands, Medical Use, Clinical Data
- Antineoplastic Agents
Brands / Synonyms
Capecitabine [Usan]; Xeloda; Xeloda
For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen.
Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of patients with metastatic breast cancer. It is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5-fluorouracil.
Mechanism of Action
Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). 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'-deaxyuridylate. 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.
Biotrnasformation / Drug Metabolism
Metabolized by thymidine phosphorylase to fluoruracil.
XELODA is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil.
The effect of an aluminum hydroxide- and magnesium hydroxide-containing antacid (Maalox)* on the pharmacokinetics
of capecitabine was investigated in 12 cancer patients. There was a small increase in plasma concentrations of
capecitabine and one metabolite (5'-DFCR); there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and
Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly
with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. Patients taking coumarin-derivative
anticoagulants concomitantly with capecitabine should be monitored regularly for alterations in their coagulation
parameters (PT or INR).
The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. Deaths from
severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin