PHARMACOKINETICS OF 5-FLUOROURACIL IN COLORECTAL-CANCER PATIENTS RECEIVING INTERFERON

Background: The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and alpha-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. Patients and methods: 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 alpha-interferon. 5-FU levels were measured by reverse-phase high performance liquid chromatography. Results: 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 alpha-interferon was administered concurrently. Conclusion: Any synergistic activity that may exist between this combination of 5-FU and alpha-interferon is not simply due to altered 5-FU pharmacokinetics.