[Mechanism and possible biochemical modulation of capecitabine (Xeloda), a newly generated oral fluoropyrimidine].
A new 5-FU analog, Capecitabine (Xeloda; N-[1-(5-deoxy-b-D-ribofuranosyl)-5-fluoro-1, 2-dihydro-2-oxo-4-pyrimidyl]-n-penyl carbamate), was generated to decrease the incidence of GI toxicity and to increase the efficacy. Capecitabine is designed as a prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR), which is clinically used for gastric, breast and colorectal cancer patients undergoing single or combination chemotherapy in Japan. Capecitabine was converted to 5'-DFUR by either human carboxyestelase or cytidine deaminase, which were mainly localized in human liver. 5'-DFUR was converted to the active form of 5-FU by thymidine phosphorylase (dThdPase) in human tumors. The expression of dThdPase was higher in malignant tumors than in noninvolved normal tissues. In this regard, a high concentration of either 5'-DFUR or 5-FU in malignant tumors may be obtained by oral administration of Capecitabine. In addition, in vivo study showed synergistic or additive effects of Capecitabine combined with anti-cancer agents (Taxanes, Mitomycin C or Cyclophosphamide), cytokines, growth factors and hormonal agents. Capecitabine may be biochemically modulated by those agents in vivo. In the results of an early phase II study on breast cancer patients in Japan, a high efficacy rate and low toxicity were observed. Also, Capecitabine was already registered as 2nd- or 3rd-line treatments for breast cancer patients by the Food & Drug Administration of the USA. Capecitabine is one of the most promising orally administered 5-FU analogs.
Saeki
T
T
Department of Surgery, National Shikoku Cancer Center Hospital, Matsuyama, Japan.
Takashima
S
S
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil