title: The feasibility of dose escalation using concurrent radiation and 5-fluorouracil therapy following pancreaticoduodenectomy for pancreatic carcinoma.
abstract: We evaluated the feasibility of dose escalation using external beam radiation therapy (RT) and 5-fluorouracil (5-FU) following pancreaticoduodenectomy for pancreatic carcinoma. Fourteen patients who underwent pancreaticoduodenectomy for stage I-III adenocarcinoma of the pancreas received postoperative high-dose chemoradiation. RT was given at 1.8-Gy daily fractions to total doses of 54 Gy for patients with negative surgical margins (n = 12), and 64.8 Gy for those with gross residual disease (n = 2). Concurrent 5-FU was given as a continuous infusion (CI) at 225 mg/m2 per day (n = 9) beginning or day 1 and continuing until the completion of RT, or by bolus injection at 500 mg/m2 per day (n = 5) during weeks 1 and 4 of RT. Follow-up ranged from 32 to 36 months (median, 35 months). All patients were able to complete the planned high-dose postoperative chemoradiation and none required a treatment break. No grade 4 acute toxicity was observed. Grade 3 acute toxicity was limited to 2 patients. Two patients developed grade 3 (n = 1) or 4 (n = 1) subacute toxicity, all gastrointestinal-related. There have been no fatal toxicities and no grade 3 or 4 late toxicity has been observed. The 3-year survival is 21%. Dose escalation of postoperative 5-FU chemoradiation following pancreaticoduodenectomy for pancreatic carcinoma is well tolerated. Further dose-intensification of postoperative adjuvant therapy in these patients appears feasible and is being evaluated in a recently activated national trial.
authors.affiliation: Department of Radiation Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536-0084, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Regine
authors.forename: W J
authors.initials: WJ
authors.lastname: John
authors.forename: P
authors.initials: P
authors.lastname: McGrath
authors.forename: W E
authors.initials: WE
authors.lastname: Strodel
authors.forename: M
authors.initials: M
authors.lastname: Mohiuddin
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000628:therapy*; D016577:Pancreaticoduodenectomy / Q000379:methods*; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil