title: Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma.
abstract: OBJECTIVE
  Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study.
  
  
  METHODS
  Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN α-2b) plus radiotherapy followed by two cycles of FU (arm A, n=64) or six cycles of FU monotherapy (arm B, n=68). One hundred ten patients (arm A, n=53; arm B, n=57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value.
  
  
  RESULTS
  Median survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P=.99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P=.49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A.
  
  
  CONCLUSIONS
  The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.
authors.affiliation: Department of Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Abel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Sabine
authors.initials: S
authors.lastname: Harig
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Detlef
authors.initials: D
authors.lastname: Bartsch
authors.forename: Justus
authors.initials: J
authors.lastname: Klein
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Reiner
authors.initials: R
authors.lastname: Kunz
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil