Accumulating data indicate a beneficial effect of combining infusional
fluorouracil (5-FU) with
radiation therapy in
gastrointestinal cancers, and phase II/III studies are under way to examine this approach in a variety of
tumor types. The oral fluoropyrimidine
capecitabine (
Xeloda) provides a more convenient approach to radiosensitization. The agent has good single-agent activity in a variety of
tumor types. The final step in activation of the
drug to
5-FU occurs via activity of
thymidine phosphorylase;
thymidine phosphorylase activity is markedly upregulated in many
tumor tissues compared with healthy tissue (Miwa M, Ura M, Nishida M, et al: Eur J
Cancer 34:1274-1281, 1998), allowing greater accumulation of
5-FU in
tumor tissue, and there is evidence indicating that
radiation therapy results in augmented upregulation of this
enzyme. A variety of data suggest benefits of
5-FU as a radiosensitizer in improving outcome of
radiation therapy in a number of
gastrointestinal cancers, including data indicating improved survival with this chemoradiation
therapy approach. Prospective and randomized studies of 5-FU-based chemoradiation are under way in esophageal, gastric, biliary tract, pancreatic, rectal, and
anal cancer. Early phase studies are planned to examine the combination of
capecitabine,
celecoxib (
Celebrex), and
radiation therapy in
esophageal cancer and
pancreatic cancer and to compare the effects of
capecitabine and
capecitabine/
oxaliplatin (
Eloxatin) with
radiation therapy in
rectal cancer. A phase III trial comparing
capecitabine and infusional
5-FU in chemoradiation
therapy in
rectal cancer has also been planned. Additional studies should be conducted in gastric, biliary tract, and
anal cancer.
Capecitabine shows promise in replacing infusional
5-FU as the platform for gastrointestinal chemoradiation
therapy.