Pilot study of continuous-infusion 5-fluorouracil, oral leucovorin, and upper-abdominal radiation therapy in patients with locally advanced residual or recurrent upper gastrointestinal or extrapelvic colon cancer

Abstract Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials: Patients with locally advanced 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 leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m 2 , with dose escalation planned in 25-mg increments, depending on patient tolerance. Results: 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 ≤3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m 2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade ≤4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); 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 toxicity developed more than one type of Grade 3 toxicity. Conclusion: In patients with upper-abdominal gastrointestinalc ancer, continuous infusion 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 toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.