Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine.
Xeloda (Capecitabine) is a fluorocytidine derivative that is selectively tumor-activated to its cytotoxic moiety, fluorouracil. Capecitabine is readily absorbed from the gastrointestinal tract. In the liver, a 60-kDa carboxylesterase(CE) hydrolyzes much of the compound to 5'-deoxy-5-fluorocytidine (5'-DFCR). Cytidine deaminase(CD), an enzyme found in most tissues, including tumors, subsequently converts 5'-DFCR to 5'-deoxy-5-fluorouridine (5'-DFUR). The enzyme thymidine phosphorylase (TP) then hydrolyzes 5'-DFUR to the active drug 5-FU. It is proved that some human carcinomas express TP in higher concentrations than surrounding normal tissues. In Japan, one of the phase 2 clinical trials tested the efficacy of twice daily oral Capecitabine at 1,657 mg/m(2)/d given for 3 weeks followed by a 1-week rest period and repeated in 4-week cycles in advanced/metastatic breast cancer patients resistant to or recurring during or after docetaxel therapy. The response rate was 20.0% (1 CR, 10 PRs). The median time to progression was 84 days and the median survival time was 452 days. The most common treatment-related adverse events throughout the phase 1 to 2 trials of capecitabine were hand-foot syndrome (50.7%), erythropenia (37.9%), lymphopenia (31.0%), hyperbilirubinemia (33.0%) and so on. Capecitabine is expected to provide a new alternative for the treatment of advanced/metastatic breast cancer.
Nishida
Masanori
M
Medical Business & Science Department 1, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D000069287:Capecitabine; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil