Investigational New Drugs

, Volume 18, Issue 4, pp 355–363 | Cite as


  • Daniel R. Budman


Drug development has undergone rapid shifts inmethodology and the use of rationally derived agents which eithertarget specific tissues or molecules such as receptors orenzymatic sites. Capecitabine is a rationally derived prodrug of5-fluorouracil which is based upon the known high concentrationof the enzyme thymidine phosphorylase in many human tumors. Thefirst prodrug designed to exploit this biochemical finding was5-DFUR which allowed cytotoxic 5-fluorouracil to bepreferentially concentrated in tumors. Unfortunately, in man thisagent was associated with significant gastrointestinal toxicity.Further manipulation of this molecular resulted in capecitabinewhich is a relatively inert prodrug, undergoes three enzymaticsteps, and offers the potential of less gastrointestinaltoxicity. Phase I trials have examined several schedules with thedivided oral daily × 14 schedule every 3 weeks as thepreferred phase II and phase III dosing method. This agentdemonstrates significant antitumor effect in diseases known tobe responsive to fluoropyrimidines. Further study is needed todetermine whether capecitabine has a broader spectrum of actionthus affecting other tumor types than 5-fluorouracil. Major doselimiting toxicities have been hand foot syndrome,nausea/vomiting, and diarrhea.

capecitabine enzymatic activation prodrug 


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Daniel R. Budman
    • 1
  1. 1.Section of Experimental Therapeutics, Don Monti Division of Oncology, North Shore University HospitalNew York University School of MedicineManhassetUSA

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