Early evaluation of abdominal/hepatic irradiation and 5-fluorouracil/leucovorin infusion after pancreaticoduodenectomy

Purpose: To describe the toxicities of a combined modality adjuvant regimen for patients with resectable periampullary adenocarcinoma. Methods and Materials: Fourteen patients with surgically resected periampullary adenocarcinoma were treated with adjuvant therapy consisting of prophylactic hepatic irradiation and pancreatic bed irradiation and concurrent infusional 5-fluorouracil and leucovorin (5-FU/LV). Starting within 60 days of surgery, patients received radiation treatments of 1.8 Gy per fraction to the liver and pancreatic bed (13 fractions), followed by 1.8 Gy per fraction to the pancreatic region (15 fractions). All radiation treatments were given with infusional 5-FU (200 mg/m²/day) and leucovorin (5 mg/m²/day) for 5 out of every 7 days during the 38-day treatment sequence. After a 1-month break, patients were scheduled to receive four cycles of infusional 5-FU/LV (2 weeks on/2 weeks off). Results: All 14 patients completed the initial combination treatment. Toxicities were tolerable; three patients had Grade 3/4 toxicities that were primarily gastrointestinal in nature. Six patients required hospitalization during therapy for treatment-related toxicities. Two patients required radiation treatment breaks of less than 1 week, and two others had radiation held for 2-4 weeks. Three patients required chemotherapy dose reductions secondary to toxicities. Toxicities in the subsequent chemotherapy-alone cycles were few and primarily manifested by Grade 2 rises in liver injury tests. Higher toxicity grades were associated with tumor progression. Twelve patients have developed recurrent disease with an equal number of recurrences occurring in the pancreatic bed as in the liver over the 12-month median follow-up. Median survival for this cohort is 417 days, not significantly different from previously reported adjuvant trials in this patient population. Conclusion: These data indicate that adjuvant therapy with concomitant large-field radiation and infusional chemotherapy is feasible and associated with manageable toxicities in patients undergoing pancreaticoduodenectomy for periampullary adenocarcinoma. Improvement in survival over other adjuvant regimens has not thus far been observed. Modification of this strategy may be required.