PROTRACTED INTRAVENOUS FLUOROURACIL INFUSION WITH RADIATION-THERAPY IN THE MANAGEMENT OF LOCALIZED PANCREATICOBILIARY CARCINOMA - A PHASE-IEASTERN-COOPERATIVE-ONCOLOGY-GROUP TRIAL

Purpose: The purpose of this study was to determine the maximum-tolera ted dose (MTD) of fluorouracil (5-FU) administered os a protracted int ravenous (IV) infusion with concurrent radiation in patients with panc reaticobiliary carcinoma. Methods: Twenty five patients with recurrent , residual, or unresectable carcinoma of the pancreas or biliary tract were treated on ct phase I trial of protracted IV infusions of 5-FU, beginning at 200 mg/m(2)/d, concurrent with radiation therapy (59.4 Gy in 33 fractions over 6 to 7 weeks). Chemotherapy began on the first d ay of radiation and continued through the entire course of treatment. After each cohort of five patients held been treated and observed, the daily dose was escalated in 25-mg/m(2) increments until dose-limiting toxicity was encountered. An additional cohort of five patients was t reated at the MTD. Clinical examination and computed tomography (CT) w ere used to evaluate response and patterns of progression. Results: Th e MTD of 5-FU was 250 mg/m(2)/d. The dose-limiting toxicity was oral m ucositis. The median survival duration of all patients treated was 11. 9 months and the 5-year survival rate was 19%. Eleven of 25 patients r emain free of local progression and four patients are without evidence of progression at 18+, 18+, 34+, and 44+ months following treatment. Conclusion: Concurrent radiation with protracted 5-FU infusion at 250 mg/m(2)/d is well tolerated and shows evidence of activity against rum ors of the pancreas and biliary system. (C) 1995 by American Society o f Clinical Oncology.