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Related Experiment Videos

Rational development of capecitabine.

M Venturini1

  • 1Divisione Oncologia Medica, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. mventur@hp380.ist.unige.it

European Journal of Cancer (Oxford, England : 1990)
|February 14, 2002
PubMed
Summary

Capecitabine, an oral chemotherapy, effectively delivers 5-fluorouracil (5-FU) to tumors. Its unique enzymatic activation targets cancer cells, showing promise in preclinical models and early clinical trials for colorectal cancer.

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Area of Science:

  • Oncology
  • Pharmacology
  • Drug Development

Background:

  • Capecitabine is an oral fluoropyrimidine carbamate.
  • It is designed to mimic continuous infusion 5-fluorouracil (5-FU).
  • Capecitabine preferentially delivers 5-FU to tumor tissue.

Purpose of the Study:

  • To evaluate capecitabine as an oral prodrug of 5-FU.
  • To determine its efficacy and safety in preclinical and early clinical settings.
  • To establish an optimal dosing regimen for metastatic colorectal cancer.

Main Methods:

  • Capecitabine undergoes a three-step enzymatic conversion to 5-FU.
  • The final activation step is dependent on thymidine phosphorylase, upregulated in tumors.
  • Preclinical xenograft models and Phase I/II clinical studies were employed.

Main Results:

  • Capecitabine demonstrated high activity in preclinical models, including 5-FU-resistant tumors.
  • Phase I studies identified the maximum tolerated dose (MTD) and feasible regimens.
  • A Phase II study established an intermittent regimen (1250 mg/m2 BID for 14 days, 7-day rest) as optimal for further development.

Conclusions:

  • Capecitabine is an effective oral prodrug of 5-FU with preferential tumor targeting.
  • The identified intermittent regimen shows promise for first-line treatment of metastatic colorectal cancer.
  • Further clinical development of capecitabine is warranted based on its activity and tolerability.

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