title: Full dose neoadjuvant FOLFIRINOX is associated with prolonged survival in patients with locally advanced pancreatic adenocarcinoma.
abstract: BACKGROUND
  The efficacy of FOLFIRINOX for metastatic pancreatic cancer has led to its use in patients with earlier stages of disease. This study retrospectively analyzed a cohort of patients with locally-advanced pancreatic cancer (LAPC) treated with FOLFIRINOX.
  
  
  METHODS
  Between 2008 and 2013, 51 treatment-naïve patients with LAPC at a single institution received first-line FOLFIRINOX with neoadjuvant intent, at the full dose as described in the PRODIGE 4/ACCORD 11 study. Combined chemoradiation was administered for those who remained unresectable after maximum response to chemotherapy. The primary outcome measure was overall survival (OS), and secondary outcomes were progression-free survival (PFS) and margin-negative (R0) resection rate, and toxicity profile.
  
  
  RESULTS
  A total of 429 cycles of FOLFIRINOX were given with a median of 8 cycles (range 2-29) per patient; 66% of cycles were full dose. After chemotherapy, 27 (53%) received chemoradiation. The median OS was 35.4 months (95% CI 25.8-45). Ten (4 borderline resectable and 6 unresectable) patients had successful R0 resections; those who had R0 resections had a significantly longer survival than those who did not (3-year OS rate 67% versus 21%, log rank p = 0.042). Increasing number of full-dose cycles was significantly associated with increased survival. The toxicity profile was similar to previous reports of this regimen.
  
  
  CONCLUSIONS
  FOLFIRINOX is feasible as neoadjuvant therapy for LAPC. Although the R0 resection rate was only 20%, the median OS of almost 3 years appears promising. Dose intensity and duration were associated with increased survival in this study, arguing against dose attenuated versions of this regimen.
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Moh'd
authors.initials: M
authors.lastname: Khushman
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Dempsey
authors.affiliation: Pontificia Universidad Javeriana, Bogota, CO, USA.
authors.forename: Jennifer Cudris
authors.initials: JC
authors.lastname: Maldonado
authors.affiliation: University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Loaiza-Bonilla
authors.affiliation: Memorial Cancer Institute, Hollywood, FL, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Velez
authors.affiliation: Florida Cancer Care, Boca Raton, FL, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Carcas
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dammrich
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Hurtado-Cordovi
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Parajuli
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Pollack
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Harwood
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Macintyre
authors.affiliation: University of Kentucky, Markey Cancer Center, Lexington, KY, USA.
authors.forename: Ching-Wei D
authors.initials: CW
authors.lastname: Tzeng
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Merchan
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Restrepo
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Ikechukwu I
authors.initials: II
authors.lastname: Akunyili
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Afonso
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Narayanan
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Portelance
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Sleeman
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Joe U
authors.initials: JU
authors.lastname: Levi
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Caio M S Rocha
authors.initials: CM
authors.lastname: Lima
authors.affiliation: University of Kentucky, Markey Cancer Center, Lexington, KY, USA. Electronic address: Peter.Hosein@uky.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hosein
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies
keywords: Borderline resectable pancreatic cancer; Chemotherapy; FOLFIRINOX; Locally advanced pancreatic cancer; Neoadjuvant; Pancreatic adenocarcinoma