5-FLUOROURACIL PLUS 5-METHYLTETRAHYDROFOLATE IN ADVANCED PANCREATIC-CANCER

A total of 20 patients with advanced pancreatic adenocarcinoma were en rolled in a phase II trial testing the activity of 5-fluorouracil give n at 370 mg/m(2) as a rapid i.v. bolus for 5 consecutive days, precede d by a rapid i.v. bolus of 200 mg/m(2) 5-methyltetrahydrofolic acid. T he treatment was repeated every 4 weeks. The median age of the patient s was 68 years and their median Eastern Cooperative Oncology Group (EC OG) performance status was 1. There were 7 patients with locally advan ced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1-7) were given, with a corr esponding dose intensity of 396 mg/m(2) per week (86% of that planned) . No complete response, 1 partial response, and 8 cases of disease sta bilization were obtained. In general the regimen was well tolerated, w ith 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-fl uorouracil appears as little effective in this disease as 5-fluorourac il plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bo lus 5-fluorouracil is so inactive as an ''effector agent'' against pan creatic cancer that its biochemical modulation with exogenous high-dos e reduced folates cannot improve the therapeutic outcome produced by t he fluoropyrimidine in these patients.