Takekazu Yamao, MD | Authors


Commentary (Yamao/Rothenberg): Coming to Grips With Hand-Foot Syndrome

August 01, 2004

Worldwide, oral fluoropyrimidineshave become attractiveoptions in the treatmentof patients with colorectal cancer.Capecitabine (Xeloda), the only commerciallyavailable oral fluorouracil(5-FU) analog in the United States,was rationally designed to provideprolonged exposure to 5-FU and togenerate 5-FU preferentially withintumor tissue.Capecitabine is absorbedunchanged through the gastrointestinalwall and is converted to 5-FU viaa three-step enzymatic cascade. It isfirst hydrolyzed in the liver by carboxylesteraseto 5'-deoxy-5-fluorocytidine(5'-DFCR). The next stepoccurs in the liver and tumor tissue,where cytidine deaminase converts5'-DFCR to 5'-deoxy-5-fluorouridine(5'-DFUR). Finally, 5'-DFUR isconverted to 5-FU by thymidinephosphorylase, which is preferentiallyexpressed in tumors