HOUSTON--A new tumor-selective agent may permit delivery of higher levels
of 5-fluorouracil (5-FU) with lower toxicity, said Richard Pazdur, MD,
of M.D. Anderson Cancer Center. A phase III trial of capecitabine is ongoing
in colorectal cancer, and it is also under study for the treatment of breast
Capecitabine, which has been developed by Hoffmann-LaRoche, is an oral
fluoropyrimidine carbamate that is preferentially converted to 5-FU at
the tumor site, Dr. Pazdur said at the Chemotherapy Foundation Symposium.
It undergoes a cascade of conversions from 5´DFCR to 5´-DFUR
and finally to 5-FU.
Its action depends on the presence of higher levels of pyrimidine nucleoside
phosphorylase in tumors than in normal tissue. Taken orally, it passes
through the intestinal mucosa intact due to its carbamate structure. It
is hoped that this will minimize the diarrhea associated with 5-FU and
doxifluridine (5´-DFUR), which releases 5-FU prodrug within the small
The phase III trial is comparing an intermittent capecitabine schedule
with IV dosing of 5-FU and leucovorin in 524 colorectal cancer patients.