Capecitabine Studied In Advanced Colon Cancer

April 1, 1997

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 cancer.

HOUSTON--A new tumor-selective agent may permit delivery of higher levelsof 5-fluorouracil (5-FU) with lower toxicity, said Richard Pazdur, MD,of M.D. Anderson Cancer Center. A phase III trial of capecitabine is ongoingin colorectal cancer, and it is also under study for the treatment of breastcancer.

Capecitabine, which has been developed by Hoffmann-LaRoche, is an oralfluoropyrimidine carbamate that is preferentially converted to 5-FU atthe tumor site, Dr. Pazdur said at the Chemotherapy Foundation Symposium.It undergoes a cascade of conversions from 5´DFCR to 5´-DFURand finally to 5-FU.

Its action depends on the presence of higher levels of pyrimidine nucleosidephosphorylase in tumors than in normal tissue. Taken orally, it passesthrough the intestinal mucosa intact due to its carbamate structure. Itis hoped that this will minimize the diarrhea associated with 5-FU anddoxifluridine (5´-DFUR), which releases 5-FU prodrug within the smallintestine.

The phase III trial is comparing an intermittent capecitabine schedulewith IV dosing of 5-FU and leucovorin in 524 colorectal cancer patients.