Treatment of colon cancer based on biochemical modulation of fluoropyrimidines by hydroxyurea.

Preclinical studies have indicated that hydroxyurea leads to enhancement of 5-fluorouracil (5-FU) activity when given after 5-FU. This is presumably due to hydroxyurea's actions resulting in maintaining low levels of deoxyuridine monophosphate pools. The combination of hydroxyurea and 5-FU has been tested in several inconclusive clinical trials in patients with advanced colorectal cancer. However, pharmacodynamic studies have been lacking, and the schedules tested have not usually tried to follow preclinical findings. With the current renewed interest in 5-FU, a role for hydroxyurea as part of its biochemical modulation is worthy of further study.