title: A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.
abstract: BACKGROUND
  Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC.
  
  
  METHODS
  AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed.
  
  
  CONCLUSIONS
  The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC.
  
  
  BACKGROUND
  AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.
authors.affiliation: Paris-Sorbonne University, UPMC University Paris 06, Paris, France. jean-baptiste.bachet@psl.aphp.fr.|Department of hepatogastroenterology, Groupe hospitalier Pitié Salpêtrière, Paris, France. jean-baptiste.bachet@psl.aphp.fr.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
authors.affiliation: Department of oncology, Hôpital Saint Antoine, Paris, France. benoist.chibaudel@sat.aphp.fr.
authors.forename: Benoist
authors.initials: B
authors.lastname: Chibaudel
authors.affiliation: Head of methodology and quality of life in oncology department, Hôpital Universitaire de Besancon, EA 3181, Besancon, France. franck.bonnetain@univ-fcomte.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of pathology, Institut Mutualiste Montsouris, Paris, France. pierre.validire@imm.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.affiliation: Department of digestive oncology, Hôpital Beaujon, Clichy, France. pascal.hammel@bjn.aphp.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.affiliation: Paris-Sorbonne University, UPMC University Paris 06, Paris, France. thierry.andre@sat.aphp.fr.|Department of oncology, Hôpital Saint Antoine, Paris, France. thierry.andre@sat.aphp.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.affiliation: Department of oncology, Institut Mutualiste Montsouris, Paris, France. christophe.louvet@imm.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
mesh_terms: D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D002985:Clinical Protocols; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D057170:Translational Research, Biomedical; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D015415:Biomarkers; D033721:Equilibrative Nucleoside Transporter 1; D003841:Deoxycytidine; D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine