title: Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial.
abstract: BACKGROUND
  In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging.
  
  
  METHODS
  Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS).
  
  
  RESULTS
  The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48% (A) and 52% (B, P = 0.81) and (y)pN0 was 30% (A) vs. 39% (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79).
  
  
  CONCLUSIONS
  This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543.
authors.affiliation: Department of Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany, henriette.golcher@uk-erlangen.de.
authors.forename: Henriette
authors.initials: H
authors.lastname: Golcher
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Brunner
authors.forename: Helmut
authors.initials: H
authors.lastname: Witzigmann
authors.forename: Lukas
authors.initials: L
authors.lastname: Marti
authors.forename: Wolf-Otto
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Christiane
authors.initials: C
authors.lastname: Bruns
authors.forename: Henry
authors.initials: H
authors.lastname: Jungnickel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Grabenbauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Susanne
authors.initials: S
authors.lastname: Merkel
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods / Q000401:mortality*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000517:prevention & control*; D010180:Pancreatectomy / Q000379:methods / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D015996:Survival Rate; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine