Pharmacokinetics of recombinant human interferon-α2a combined with 5-fluorouracil in patients with advanced colorectal carcinoma

We evaluated the pharmacokinetics of 5-fluorouracil (5-FU) combined with recombinant human interferon (IFN)-alpha 2a in 10 previously untreated patients with advanced colorectal carcinoma. 5-FU was administered as a continuous i.v. infusion, 750 mg/m(2)/day for 5 days during week 1. One s.c. injection of IFN-alpha 2a, 9 x 10(6) IU, was administered during week 2. Beginning with week 3, a continuous i.v, infusion of 5-FU 750 mg/m(2)/day for 5 days was administered in combination with IFN-alpha 2a, 9 x 10(6) IU s.c. three times per week. The combination of 5-FU and IFN-alpha 2a was continued every other week until either 3 months after complete remission or tumor progression. No grade 4 toxicity was observed. Granulocytopenia (two patients), leukopenia tone patient), thrombocytopenia tone patient), stomatitis (two patients), fatigue tone patient) and hand-foot syndrome tone patient) were the major (grade 3) toxic reactions encountered. Overall, one complete and six partial responses were noted, The results of the paired t-test showed no statistically significant differences between the means of the two treatments, 5-FU and 5-FU plus IFN-alpha 2a, with respect to the steady-state plasma concentration, area under the concentration-time curve, total body clearance, or steady-state volume of distribution of 5-FU, or the serum concentration of IFN, We conclude that 5-FU and IFN-alpha 2a do not interact pharmacokinetically at the doses and schedules in the regimen studied, [(C) 1998 Lippincott Williams & Wilkins.].