Modulation of 5-FU/alpha-interferon with high-dose continuous infusion hydroxyurea

Biochemically modulated 5-fluorouracil (5-FU) regimens are active against several gastrointestinal malignancies. Hydroxyurea is an inhibitor of the enzyme ribonucleotide reductase. Despite successful in vitro studies, studies combining oral hydroxyurea with 5-FU based regimens have failed to demonstrate clinical synergy. Based on the pharmacokinetic properties of hydroxyurea, continuous exposure to the drug may be required to reproduce the synergy observed in vitro. We will review the pharmacology of hydroxyurea and the rationale for the modulation of 5-FU/alpha-interferon (IFN) with high-dose continuous infusion hydroxyurea.