Fluorouracil plus interferon + folinic acid in regional and systemic therapy in colorectal cancer

Modulation of fluorouracil (5-FU) therapy with folinic acid (FA) in advanced colorectal adenocarcinoma produces a doubled increase in remission rates, but one important study with another modulation of 5-FU with interferon alfa 2a (IFN-alpha-2a) had better results. In the fact that both modulations have different mechanisms of interaction, it seems hopeful that both have additive or synergistic effects and they give further increases of remission rates. Twenty-three patients with proven progressive advanced colorectal cancer were treated with 5-FU, FA, and IFN-alpha-2a in three different regimens. IFN-alpha-2a was given subcutaneously in a dose of 5 MioU per day during 5-FU treatment. In the first regimen FA (500 mg/m2) was administered in a short time infusion (30 minutes) while 5-FU (1,000 mg/m2) was given in a 24-hour continuous infusion with weekly intervals. In regimen 2 and 3 FA/5-FU treatment was given on days 1 to 5 every 3 to 4 weeks. The difference was time and dose of the 5-FU infusion (600 mg/m2 in 4-hour versus 350 mg/m2 by push injection). Three patients with isolated liver metastases and one patient with local recurrence of rectal carcinoma received regional therapy with higher 5-FU doses. Dose escalation was carried out in all regimens when possible (toxicity less than or equal to World Health Organization [WHO] grade 1). Objective response rates were reached in nine of 23 patients with two complete remissions (one in regional and systemic treatment) with a mean duration of 6 months. Eight patients had stable disease and six had therapy failure. In pretreated patients no complete remission was reached; three of seven had partial remission, two no change, and two progressive disease. Severe toxicity occurred in 12 of 23 patients with mucositis WHO grade 4 in one patient, grade 3 in two, hematotoxicity grade 3 in three, and cutaneous toxicity in two. Eight of twenty-three patients had alopecia grades 2 and 3. These early results of our phase II study with limited patients shows no significant advantage of double modulation in comparison to the well established results of FA/5-FU therapy.