title: Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study.
abstract: OBJECTIVE
  To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA).
  
  
  METHODS
  Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).
  
  
  RESULTS
  Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL.
  
  
  CONCLUSIONS
  With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial.
authors.affiliation: Department of Medical Oncology, Centre Alexis Vautrin, 54511 Vandoeuvre-lès-Nancy Cedex, France. t.conroy@nancy.fnclcc.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.forename: Bernard
authors.initials: B
authors.lastname: Paillot
authors.forename: Eric
authors.initials: E
authors.lastname: François
authors.forename: Roland
authors.initials: R
authors.lastname: Bugat
authors.forename: Jacques-Henri
authors.initials: JH
authors.lastname: Jacob
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stein
authors.forename: Salvador
authors.initials: S
authors.lastname: Nasca
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Metges
authors.forename: Olivier
authors.initials: O
authors.lastname: Rixe
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Magherini
authors.forename: Aliette
authors.initials: A
authors.lastname: Hua
authors.forename: Gael
authors.initials: G
authors.lastname: Deplanque
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D016019:Survival Analysis
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D002166:Camptothecin