A phase I trial of 5-fluorouracil, leucovorin and interferon-alpha 2b administered by 24h infusion in metastatic colorectal carcinoma

A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m(2) administered concomitantly with LV at 500 mg/m(2) over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m(2)). The maximum tolerated dose of IFN was 18 MU/m(2). At 27 MU/m(2) two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m(2)). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m(2) given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.