title: Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.
abstract: OBJECTIVE
  Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown.
  
  
  METHODS
  Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy.
  
  
  RESULTS
  There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001).
  
  
  CONCLUSIONS
  Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.
authors.affiliation: Juan W. Valle, Derek O'Reilly, Manchester Academic Health Sciences Centre, Christie Hospital NHS Foundation Trust and University of Manchester, Manchester; Richard Jackson, Trevor Cox, John P. Neoptolemos, Paula Ghaneh, Charlotte L. Rawcliffe, Liverpool Cancer Research UK Centre and the National Institute for Health Research Pancreas Biomedical Research Unit, University of Liverpool, Liverpool; Daniel Palmer, the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust; Deborah D. Stocken, the Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham; David Cunningham, Royal Marsden Hospital Foundation Trust, Sutton; Mark R. Middleton, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford; Alan Anthoney, The Leeds Teaching Hospital Trust, Leeds; Kate Sumpter, Freeman Hospital, Newcastle upon Tyne; Ross Carter, Glasgow Royal Infirmary, Glasgow, United Kingdom; Claudio Bassi, Giovanni Butturini, University of Verona, Verona, Italy; David Goldstein, Bridget A. Robinson, Christos Karapetis, the Australasian Gastro-Intestinal Trials Group, Camperdown, Australia; Andrew Scarfe, University of Alberta, Edmonton, Canada; Francois Lacaine, Hôpital TENON, Assistance Publique Hôpitaux de Paris, Universite Pierre Et Marie Curie, Paris, France; Juhani Sand, Tampere University Hospital, Tampere, Finland; Jakob R. Izbicki, University of Hamburg, Hamburg; Julia Mayerle, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald; Markus W. Büchler, University of Heidelberg, Heidelberg, Germany; Christos Dervenis, the Agia Olga Hospital, Athens, Greece; Attila Oláh, the Petz Aladar Hospital, Gyor, Hungary; Pehr A. Lind, Karolinska-Stockholm Söder Hospital, Stockholm, Sweden.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.forename: Daniel
authors.initials: D
authors.lastname: Palmer
authors.forename: Richard
authors.initials: R
authors.lastname: Jackson
authors.forename: Trevor
authors.initials: T
authors.lastname: Cox
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Rawcliffe
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassi
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Stocken
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Derek
authors.initials: D
authors.lastname: O'Reilly
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Robinson
authors.forename: Christos
authors.initials: C
authors.lastname: Karapetis
authors.forename: Andrew
authors.initials: A
authors.lastname: Scarfe
authors.forename: Francois
authors.initials: F
authors.lastname: Lacaine
authors.forename: Juhani
authors.initials: J
authors.lastname: Sand
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: Christos
authors.initials: C
authors.lastname: Dervenis
authors.forename: Attila
authors.initials: A
authors.lastname: Oláh
authors.forename: Giovanni
authors.initials: G
authors.lastname: Butturini
authors.forename: Pehr A
authors.initials: PA
authors.lastname: Lind
authors.forename: Mark R
authors.initials: MR
authors.lastname: Middleton
authors.forename: Alan
authors.initials: A
authors.lastname: Anthoney
authors.forename: Kate
authors.initials: K
authors.lastname: Sumpter
authors.forename: Ross
authors.initials: R
authors.lastname: Carter
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D016019:Survival Analysis; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine