PILOT-STUDY OF CONTINUOUS-INFUSION 5-FLUOROURACIL, ORAL LEUCOVORIN, AND UPPER-ABDOMINAL RADIATION-THERAPY IN PATIENTS WITH LOCALLY ADVANCEDRESIDUAL OR RECURRENT UPPER GASTROINTESTINAL OR EXTRAPELVIC COLON-CANCER

Purpose: The purpose of this study,vas to develop a satisfactorily tol erated regimen of radiation therapy, continuous infusion 5-fluorouraci l, and leucovorin in patients with locally advanced upper-abdominal ga strointestinal cancer. Methods and Materials: Patients with locally ad vanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4-9 Gy in three to five fractions to the tumor. Treatment with leuc ovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was a dministered at an initial daily dose of 125 mg/m(2), with dose escalat ion planned in 25-mg increments, depending on patient tolerance. Resul ts: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m(2). One patient experienced Grade 4 anorexia and nausea. No other Grade greate r than or equal to 3 toxicity was observed at this dose. Fifteen evalu able patients were entered at a planned 5-fluorouracil dose of 150 mg/ m(2) daily; 6 of them experienced Grade 3 toxicity, and none experienc ed Grade greater than or equal to 4 toxicity. Grade 3 toxicities and t he number of patients who developed each were: vomiting (three patient s); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxici ty developed more than one type of Grade 3 toxicity. Conclusions: In p atients with upper-abdominal gastrointestinal cancer, continuous infus ion 5-fluorouracil (150 mg/m(2) daily), leucovorin (10 mg orally daily ), and radiation therapy (50-54 Gy) resulted in a 40% rate of severe t oxicity but no life-threatening toxicity. This clinical trial excludes , with 90% confidence, a 20% risk of Grade 4 toxicity with this combin ation. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose. (C) 1997 Elsevier Scienc e Inc.