DIFFERENT DOSE REGIMENS OF 5-FLUOROURACIL AND INTERFERON-ALPHA IN PATIENTS WITH METASTATIC COLORECTAL-CARCINOMA

Three different 5-fluorouracil (5-FU)-interferon-alpha-2b (IFN)-contai ning regimens were designed for treatment of patients with advanced co lorectal cancer. 87 patients with a Karnofsky index greater than or eq ual to 70 were included in three sequential non-randomised phase II tr ials. Regimen A consisted of 5-FU (750 mg/m(2)/day) given as a continu ous infusion on days 1-5 followed by weekly 1-h intravenous infusions until week 8. IFN (5 MU) was given subcutaneously on days 1, 3 and 5 f ollowed by injections (9 MU) every second day until week 8. The cycle was then repeated. Regimen B consisted of 5-FU (750 mg/m(2)/day) given as a continuous infusion on days 1-5 followed by 5-min intravenous in jections on days 12 and 19. IFN (3 MU) was given subcutaneously on day s 1-5 followed by injections (5 MU) on days 11-13 and 18-20. The cycle was repeated every fourth week. Regimen C consisted of 5-FU (750 mg/m (2)/day) given as a continuous infusion on days 1-5. IFN (3 MU) was gi ven subcutaneously on days 1-5. The cycle was repeated every third wee k, The objective response rates (complete response (CR) and partial re sponse (PR)) after approximately 4 months of therapy or longer were as follows: regimen A (n = 27) 22% (2 CR, 4 PR), regimen B (n = 33) 42% (4 CR, 10 PR) and regimen C (n = 27) 22% (1 CR, 5 PR). The correspondi ng response figures for previously untreated patients were regimen A 5 0%, regimen B 64% and regimen C 38%. Response durations varied from a few weeks up to 142 + weeks. Toxicities were generally mild and revers ible, and the treatments were convenient for the patients and cost eff ective since the 5-day infusions could be given by a portable pump wit hout hospitalisation. Our results are in agreement with those of other s showing that 5-FU/IFN combinations can be highly effective in advanc ed colorectal canter, and that a number of factors such as doses, dose intensities, infusion rates and timing of the two drugs may be crucia l for the antitumour activity of this drug combination.