ORLANDOCapecitabine (Xeloda) might one day replace infusional fluorouracil(Drug information on 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(Drug information on 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.