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Translational Research, Early Clinical Trials Support Xeloda/RT in GI Cancers

Translational Research, Early Clinical Trials Support Xeloda/RT in GI Cancers

ORLANDO—Capecitabine (Xeloda) might one day replace infusional
fluorouracil (5-FU) as a radiosensitizing platform in the chemoradiation of
advanced gastrointestinal malignancies, according to Tyvin A. Rich, MD,
professor of radiation oncology, University of Virginia Health Sciences
Center, Charlottesville. The oral fluoropyrimidine simplifies
chemoradiation, is well tolerated, and is highly appealing to patients and
physicians alike, he said.

Speaking at an industry-sponsored symposium held in conjunction with the
ASCO meeting, Dr. Rich reviewed results with 5-FU and radiation therapy
(generally in the range of 45 to 55 Gy) in esophageal, gastric, biliary,
pancreatic, and rectal cancers.

With a 5-FU/radiation therapy combination, Dr. Rich said, approximately
25% of patients with esophageal cancer now achieve a 5- to 10-year cure. A
phase III trial of bolus 5-FU/leucovorin and radiation therapy in gastric
cancer, which was reported by the Southwest Oncology Group last year,
achieved cures in about 50% of patients.

Dr. Rich’s group is now taking the 5-FU/radiation therapy data and
looking at new agents and new combinations, including radiation therapy plus
capecitabine.

Capecitabine is a logical choice to pair with radiation therapy for
several reasons, he said. The drug itself is active, it is well tolerated
with radiation therapy, and it has a three-step metabolism that involves
thymidine phosphorylase, which ultimately leads to concentration of 5-FU in
the tumor. Moreover, preclinical data indicate that radiation therapy
upregulates thymidine phosphorylase.

"So we may be able to target the cancer and turn on something that
makes the drug a little bit more effective," Dr. Rich said. "We
haven’t proved this in a clinical setting, and I think it’s going to be
a long time before we’ll have those kind of data, but translational
research would lead us to believe that this may be the case."

A phase I German study of capecitabine plus radiation in patients with
rectal cancer (Dunst J et al: Proc Am Assoc Clin Oncol 2001, abstract 592)
concluded that 825 mg/m² of capecitabine bid on days 1 to 7 each week along
with 50 to 59 Gy of radiation therapy was well tolerated.

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