Background: To evaluate the therapeutic activity of 24-hour continuously infused 5-fluorouracil (5-FU) modulated by high-dose folinic acid in patients with metastatic colorectal cancer who had recurred or progressed following mainly bolus 5-FU/folinic acid chemotherapy, Patients and Methods: Forty-two patients with a median age of 59 years (45-76) were enrolled, Karnosfky status was 90% (80-100), previous chemotherapy regimen bolus 5-FU/folinic acid (n = 33, 79%) or 24-hour continuous 5-FU +/- interferon at (n = 9, 21%). Chemotherapy was given as a weekly infusion of 500 mg/m(2) folinic acid over 2 h followed by a 24-hour continuous infusion of 2,600 mg/m(2) 5-FU for 6 consecutive weeks followed by a 2-week rest period. Results: No complete but 6 partial responses were observed (ORR: 14%, CI95%: 3.5-25.1%) with a median response duration of 7.3 months (range: 1,4-10.6), The median survival from the start of continuous infusion of 5-FU was 1 1.6 months (range: 2-27, CI95%: 9,4-13.8) and the 1-year survival rate was 46%, Disease stabilization and minor responses were achieved in another 25 patients (61%). WHO grade III/IV diarrhea occurred in 26% of patients, mucositis, nausea/vomiting and hand-foot syndrome in 5% each. Two cases of WHO grade III anemia and leukocytopenia were observed (5% each), Dose reductions had to be performed in 1 1 patients because of unacceptable diarrhea with subsequent stop of treatment in 2 patients, Progressive disease while receiving previous bolus 5-FU chemotherapy was associated with a lower response rate, shorter progression-free interval and overall survival compared to response and survival of patients who had achieved temporary disease stabilization during previous bolus 5-FU therapy, Conclusions: Continuous infusion of 5-FU/folinic acid displays activity in pretreated and refractory colorectal cancer with acceptable toxicity, Patients who had achieved disease stabilization or objective remission with previous 5-FU bolus therapy appear to be more likely to benefit from second-line treatment. Questions remaining to be addressed include the optimal starting dose of continuously infused 5-FU and whether the dose of folinic acid can be reduced or completely eliminated with respect to toxicity and health economics.
