MODULATION OF 5-FLUOROURACIL WITH METHOTREXATE AND LOW-DOSE N-(PHOSPHONACETYL)-L-ASPARTATE (PALA) IS INACTIVE IN ADVANCED PANCREATIC-CARCINOMA

Purpose. To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in p atients with advanced pancreatic adenocarcinoma, Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m(2) i.v. 15-minute infusion followed by methotrexate 200 mg/m (2) i,v. 30-minute infusion on day 1 and 5-FU 600 mg/m(2) i,v. push on day 2, Folinic acid was given at 15 mg/m(2) p,o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles wer e repeated every two weeks. Results. Thirty patients with advanced che motherapy-naive pancreatic cancer were included; 26 had measurable dis ease. Median age 56 years (27-72); median PS 1 (0-2). One PR (3.9%) wa s achieved; nine patients had stable disease. Median time to progressi on was 91 days, Median survival was 177 days and one year survival was 13.3% (4 of 30 patients), Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients, Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with a dvanced pancreatic adenocarcinoma.