Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial.

Abstract

PURPOSE The purpose of this study was to determine the maximum-tolerated dose (MTD) of fluorouracil (5-FU) administered as a protracted intravenous (IV) infusion with concurrent radiation in patients with pancreaticobiliary carcinoma. METHODS Twenty-five patients with recurrent, residual, or unresectable carcinoma of the pancreas or biliary tract were treated on a phase I trial of protracted IV infusions of 5-FU, beginning at 200 mg/m2/d, concurrent with radiation therapy (59.4 Gy in 33 fractions over 6 to 7 weeks). Chemotherapy began on the first day of radiation and continued through the entire course of treatment. After each cohort of five patients had been treated and observed, the daily dose was escalated in 25-mg/m2 increments until dose-limiting toxicity was encountered. An additional cohort of five patients was treated at the MTD. Clinical examination and computed tomography (CT) were used to evaluate response and patterns of progression. RESULTS The MTD of 5-FU was 250 mg/m2/d. The dose-limiting toxicity was oral mucositis. The median survival duration of all patients treated was 11.9 months and the 2-year survival rate was 19%. Eleven of 25 patients remain 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/m2/d is well tolerated and shows evidence of activity against tumors of the pancreas and biliary system.