[Mechanism and possible biochemical modulation of capecitabine (Xeloda), a newly generated oral fluoropyrimidine]

Gan To Kagaku Ryoho. 1999 Mar;26(4):447-55.
[Article in Japanese]

Abstract

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.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Capecitabine
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Colorectal Neoplasms / drug therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Administration Schedule
  • Female
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Stomach Neoplasms / drug therapy

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil