Dose-intensive chemoradiation following pancreaticoduodenectomy for pancreatic carcinoma - a phase I study

Purpose/Objective: To prospectively evaluate the feasibility and toxicity of high-dose external beam radiation therapy (RT) and concurrent continuous infusion (CI) 5-Fluorouracil (5-FU) in patients following pancreaticoduodenectomy for pancreatic carcinoma. Materials and Methods: Fifteen patients who underwent pancreaticoduodenectomy for stage I-III adenocarcinoma of the pancreas between January, 1994 and November, 1995 were entered into this phase I study of postoperative dose-intensive chemoradiation. Planned treatment was non-split course RT given at 1.8 Gy daily fractions to total doses of 54 Gy for patients with negative surgical margins (N=12), 59.4 Gy for those with positive margins (N=2) and 64.8 Gy for those with gross residual (N=1). Concurrent 5-FU was given without interruption throughout the course of RT as a CI at 225 mg/m2/d. The National Cancer Institute common toxicity criteria were used in assessment of adverse effects. Grade 1, 2, 3, 4, and 5 correspond to mild, moderate, severe, life-threatening, and fatal toxicity, respectively. Toxicities were classified as acute (during chemoradiation), subacute (up to 6 months following chemoradiation), and late (> 6 months following chemoradiation). Follow-up ranges from 2-20 months (median = 8 months). Results: All patients were able to complete planned dose-intensive chemoradiation and none required a treatment break. No grade 4 acute toxicity was observed. Grade 3 acute toxicity was limited to a single patient who required hospitalization for hypotension related to dehydration. Three patients (21%) developed Grade 3 (N=2) or 4 (N=1) subacute toxicity, all gastrointestinal related. There have been no fatal toxicities. Only 2 patients have died of disease and no grade 3 or 4 late toxicity has been observed. Conclusion: This postoperative dose-intensive chemoradiation protocol, following pancreaticoduodenectomy for pancreatic carcinoma, is acutely very well tolerated. Assessment of subacute and late toxicity, as well as survival, awaits further follow-up and will be presented. In the meantime, escalation of the dose of concurrent CI 5-FU to 250 mg/m2/d is being evaluated for use in our next cohort of patients