Fluoropyrimidine-Radiation Interactions in Cells and Tumors

The fluoropyrimidines (fluorodeoxyuridine [FdUrd] and fluorouracil [5-FU] are potent radiation sensitizers. This article summarizes recent data concerning potential mechanisms of fluoropyrimidine-radiation interactions at the cellular and tumoral level. Evidence now suggests cells can be radiosensitized when exposed to the fluoropyrimidines either before or after radiation but by different mechanisms. Sensitization is not explained by redistribution of cells into a sensitive phase of the cell cycle. Rather, cells that are exposed to FdUrd before radiation progress in S phase in the presence of fluoropyrimidines and are radiosensitized. Radiation can also increase the anabolism of 5-FU into the toxic metabolite and decrease drug clearance from the tumor. These laboratory data may aid in the design of clinical trials combining radiation and fluoropyrimidines.