title: Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study).
abstract: BACKGROUND
  Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.
  
  
  METHODS
  This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m(2)) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.
  
  
  CONCLUSIONS
  The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.
  
  
  BACKGROUND
  clinicalTrials.gov NCT01314027.
authors.affiliation: Department of General and Abdominal Surgery, University Hospital of Mainz, Langenbeck-strasse 1, 55118 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Heinrich
authors.forename: Bernhard
authors.initials: B
authors.lastname: Pestalozzi
authors.forename: Mickael
authors.initials: M
authors.lastname: Lesurtel
authors.forename: Frederik
authors.initials: F
authors.lastname: Berrevoet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Laurent
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Delpero
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
authors.forename: Phillippe
authors.initials: P
authors.lastname: Bachellier
authors.forename: Patrick
authors.initials: P
authors.lastname: Dufour
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Xavier
authors.initials: X
authors.lastname: Rogiers
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D057170:Translational Research, Biomedical; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000093542:Gemcitabine