Pharmacokinetics of 5-fluorouracil in colorectal cancer patients receiving interferon

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Abstract
The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and α-interferon in colorectal cancer have suggested better response rates. One possible explanation for interaction between 5-FU and interferon is that interferon alters the pharmacokinetics of 5-FU, increasing plasma 5-FU levels. To investigate the possibility of interaction between the two agents, steady state 5-FU pharmacokinetics was evaluated in patients with colorectal cancer who received 5-FU by continuous i.v. infusion with and without concurrent administration of subcutaneous α-interferon. 5-FU levels were measured by reverse-phase high-performance liquid chromatography. Twenty-six patients were evaluated. There were 4 partial responses (15%). There was no significant difference in steady state 5-FU levels whether or not α-interferon was administered concurrently. Any synergistic activity that may exist between this combination of 5-FU and α-interferon is not simply due to altered 5-FU pharmacokinetics.