Bimonthly high dose leucovorin and 5-fluorouracil 48-hour infusion with interferon-alpha-2a in patients with advanced colorectal carcinoma

BACKGROUND. The rationale for the modulation of 5-fluorouracil (5-FU) with interferon-alpha (IFN) is inhibition of 5-FU catabolism and 5-FU resistance. Clinical trials have shown debatable results when IFN is given in high doses with 5-FU used as a bolus alone or in combination with leucovorin (LV), A first-line Phase II study was performed in 50 patients with metastatic colorectal carcinoma who were given a bimonthly combination of high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN. METHODS. The regimen was comprised of a 2-hour infusion of LV, 500 mg/m(2), on each of 2 consecutive days, and a 48-hour infusion of 5-FU, 1.5 to 2 g/m(2)/24 hours, starting after Day 1 of LV treatment every 2 weeks until there was evidence of disease progression. IFN was administered subcutaneously three times weekly at a dose of 3 MU (body surface area [BSA] < 1.75 m(2)) or 4.5 MU (BSA greater than or equal to 1.75 m(2)). RESULTS, World Health Organization toxicity Grade 3-4 occurred in 21 patients (42%): diarrhea in 6%, mucositis in 12%, neutropenia in 30%, and alopecia in 8%. The overall response rate was 44%; 1 patient had a complete response (2%), 21 had partial responses (42%), 23 had stable disease (46%), and 5 had disease progression (10%). The median progression free survival was 9 months, and median survival was 25 months. CONCLUSIONS, Bimonthly high dose LV, a high dose 48-hour infusion of 5-FU, and a low dose of IFN had good activity in patients with advanced colorectal carcinoma, However, as in other schedules of LV and 5-FU, IFN induces high grade toxicity. (C) 1997 American Cancer Society.