Increasing doses of 5-fluorouracil and high-dose folinic acid in the treatment of metastatic colorectal cancer

Aims and background: Combined B-fluorouracil (5FU) and folinic acid (FA) is the first-line treatment of metastatic colorectal cancer. The aims of this study were to individualize the dose of 5FU in a weekly schedule in which the maximum tolerated dose of 5FU is administered to each patient, and to e valuate the impact of increasing 5FU doses on response and survival, Method s: Thirty-two patients (30 evaluable for response) with metastatic colorect al cancer were treated with weekly intravenous doses of FA 150 mg/m(2) and a fast infusion of 5FU, at an initial dose of 600 mg/m(2) which was increas ed by 60 mg/m2 every week until the appearance of a side effect, in order t o determine the maximum tolerated dose for the patient, Results: We obtaine d 11 objective responses (36.7%, median survival 22 months) and 15 disease stabilizations (50%, median survival 15 months); there were four cases of p rogressive disease (13.3%, median survival 4 months). The overall survival was 15 months. Twenty-eight patients (87.5%) tolerated 5FU doses of 720 mg/ m(2) or more. Conclusions: Weekly 5FU with high-dose FA modulation can be i ndividualized by dose escalation. A 5FU dose of 720 mg/m2 per week seems to be critical, as higher doses are no more effective and lead to severe side effects, This schedule gives good results in terms of response, even thoug h the complete response rate remains low.