5-Fluorouracil plus 5-methyltetrahydrofolate in advanced pancreatic cancer. GLISP (Gruppo Ligure Studio Pancreas)

A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a rapid i.v. bolus for 5 consecutive days, preceded by a rapid i.v. bolus of 200 mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The median age of the patients was 68 years and their median Eastern Cooperative Oncology Group (ECOG) performance status was 1. There were 7 patients with locally advanced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1-7) were given, with a corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No complete response, 1 partial response, and 8 cases of disease stabilization were obtained. In general the regimen was well tolerated, with only 2 patients suffering from grade 3 stomatitis or diarrhea; the most common toxicity was nausea, which was experienced by almost 50% of the patients. The combination of 5-methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bolus 5-fluorouracil is so inactive as an "effector agent" against pancreatic cancer that its biochemical modulation with exogenous high-dose reduced folates cannot improve the therapeutic outcome produced by the fluoropyrimidine in these patients.