title: Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm?
abstract: BACKGROUND
  Borderline resectable pancreatic cancer is best treated by multimodality therapy. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) tripled the response rate and significantly increased median survival for patients with advanced pancreatic cancer and shows promise for neoadjuvant use. Toxicity concerns prompted a careful analysis of our initial FOLFIRINOX experience.
  
  
  METHODS
  All patients diagnosed with borderline resectable, biopsy-proven pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX between July 2010 and December 2012 were reviewed. Primary outcome was surgical resectability. Secondary outcomes were treatment-related toxicities and survival.
  
  
  RESULTS
  FOLFIRINOX followed by gemcitabine- or capecitabine-based chemoradiation was initiated in 18 patients. The most common grade 3 or 4 toxicities during chemotherapy were gastrointestinal, including nausea/emesis (n = 5), weight loss (n = 3) and diarrhea (n = 2), and hematologic (n = 2; neutropenia); five patients (36%) required a total of six admissions. Neoadjuvant therapy was completed in 15 of 18 patients (83%), and 12 (67%) underwent pancreatectomy (10 Whipple, 2 total pancreatectomy) including portal vein resection/reconstruction in 10 (83%). Disease progression precluded surgery in 6 of the 18 patients (33%). All 12 resected patients had negative (R0) margins. Only 2 of 12 (17%) were node positive (median node count: 26.5 [range: 15-39]). There were no in-hospital or 30-day mortalities and no clinical pancreatic leaks or reoperations. Of the 12 patients who completed all intended therapy, 7 (58.3%) are alive, including 5 who have no evidence of disease (median months from diagnosis: 22 months [range: 18-35 months). The six patients who did not complete all planned therapy are deceased (months from diagnosis: 6.9-17.5 months).
  
  
  CONCLUSIONS
  FOLFIRINOX followed by chemoradiation as neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma is safe, and our initial experience suggests favorable resection rates compared with previous reports in this high-risk patient population.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Department of Medicine, Division of Medical Oncology, and Department of Radiation Oncology, Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Christians
authors.forename: Susan
authors.initials: S
authors.lastname: Tsai
authors.forename: Anna
authors.initials: A
authors.lastname: Mahmoud
authors.forename: Paul
authors.initials: P
authors.lastname: Ritch
authors.forename: James P
authors.initials: JP
authors.lastname: Thomas
authors.forename: Lauren
authors.initials: L
authors.lastname: Wiebe
authors.forename: Tracy
authors.initials: T
authors.lastname: Kelly
authors.forename: Beth
authors.initials: B
authors.lastname: Erickson
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Evans
authors.forename: Ben
authors.initials: B
authors.lastname: George
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine
keywords: Borderline resectable pancreas cancer; FOLFIRINOX; Neoadjuvant therapy; Pancreatic adenocarcinoma