title: Adjuvant interferon-based chemoradiation followed by gemcitabine for resected pancreatic adenocarcinoma: a single-institution phase II study.
abstract: OBJECTIVE
  This is a phase II, single-center, single-arm study of patients with resectable adenocarcinoma of the pancreas who were treated with adjuvant interferon-based chemoradiation followed by gemcitabine. The primary end point was 2-year overall survival, with secondary endpoints being 2-year disease-free survival, and the frequency of grade 3 or 4 toxicity.
  
  
  METHODS
  From April 2002 to September 2005, 53 patients with adenocarcinoma of the pancreas underwent curative resection at a single institution, and subsequently received interferon- and gemcitabine-based adjuvant therapy consisting of external-beam irradiation at a dose of 5040 cGy (25 fractions per 5 weeks) and simultaneous 3-drug chemotherapy consisting of (1) continuous infusion 5-fluorouracil (175 mg/m2); (2) weekly intravenous bolus cisplatin (25 mg/m2); and (3) interferon-alpha (3 million units subcutaneously 3 times per week) during the 6 weeks of radiation. This was followed by two 4-week courses of weekly intravenous infusion of gemcitabine (1000 mg/m2, 3 of 4 weeks).
  
  
  RESULTS
  Median follow-up is 38 months. Seventy-seven percent of patients had node-positive disease. Sixteen patients (30%) failed to complete adjuvant therapy, due to disease progression (7 patients), toxicity (7 patients), and consent withdrawal (2 patients). No patients completed planned therapy without dose modification. Median overall survival was 25 months (confidence interval [CI] = 21.5-48.5 months). Actuarial overall survival for the 1-, 2- and 3-year periods were 75% (CI = 61-85%), 56% (CI = 41-69%), and 41% (26-55%), respectively.
  
  
  CONCLUSIONS
  This phase II trial demonstrated increased patient survival compared with historical controls, and equivalent survival compared with the regimen combining interferon-alpha with 5-fluorouracil-based chemoradiation. Despite these encouraging results, significant concerns regarding dose- and treatment-limiting toxicities remain.
authors.affiliation: Department of Surgery, Barnes-Jewish Hospital/Washington University Medical Center and Siteman Cancer Center, St Louis, Missouri 63110, USA. linehand@wustl.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Linehan
authors.forename: Marcus C B
authors.initials: MC
authors.lastname: Tan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Strasberg
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Drebin
authors.forename: William G
authors.initials: WG
authors.lastname: Hawkins
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Malyapa
authors.forename: Michael
authors.initials: M
authors.lastname: Hull
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Tan
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011336:Probability; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine