title: Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer.
abstract: BACKGROUND
  Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.
  
  
  METHODS
  Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined.
  
  
  RESULTS
  In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65-14.32) and PFS 6.1 months (95% CI 5.19-8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0-23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001) and fatigue (P=0.01) were significantly decreased. [(18)F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS.
  
  
  CONCLUSIONS
  In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Stein
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: James
authors.affiliation: Yale School of Public Health, 300 George Street, New Haven, CT 06510, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Yale School of Public Health, 300 George Street, New Haven, CT 06510, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Kortmansky
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.|VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Staugaard
authors.affiliation: Department of Diagnostic Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Doddamane
authors.initials: D
authors.lastname: Indukala
authors.affiliation: Department of Diagnostic Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Boustani
authors.affiliation: Department of Diagnostic Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Vatsal
authors.initials: V
authors.lastname: Patel
authors.affiliation: Department of Surgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cha
authors.affiliation: Department of Surgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Salem
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
authors.affiliation: Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Lacy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin