title: Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM).
abstract: BACKGROUND
  Fluorouracil and irinotecan-based, and gemcitabine-based regimens, are the standard of care in the first-line treatment of patients with metastatic pancreatic cancer. New approaches are needed to improve survival and quality of life. Whether a sequential approach alternating irinotecan, fluorouracil and gemcitabine may be effective and tolerable in patients with metastatic pancreatic cancer is unknown.
  
  
  METHODS
  In this randomised, multicentre, open-label, phase 2 trial, patients with metastatic pancreatic adenocarcinoma, World Health Organisation (WHO) performance status 0-1, and bilirubin levels <1.5 upper limit of normal values (ULN) were randomised 1:1 to receive as first-line treatment either FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) alternating with fixed-dose rate gemcitabine as 2-month periods (FIRGEM, arm A), or fixed-dose rate gemcitabine alone (arm B). Treatment was continued until disease progression or limiting toxicity. The primary end-point was the crude progression-free survival (PFS) rate at 6 months. The study is registered with EudraCT (N° 2006-005703-34).
  
  
  RESULTS
  Between October 2007 and March 2011, 98 patients were enroled. The observed 6-month PFS rate was 43.5% (95% confidence interval (CI), [28.6-58.4%]) in arm A reaching the Fleming decision rules criteria to reject H0 and 26.1% (95% CI [12.9-39.3%]) in arm B. Objective response rates were 37% (23-51%) in arm A and 10% (1-19%) in arm B. Median PFS (5.0 versus 3.4 months, hazard ratio (HR)=0.59 [0.38-0.90]) and overall survival (11.0 versus 8.2 months, HR=0.71 [0.46-1.10]) were higher in arm A compared to arm B. The most frequent grade 3-4 toxicities were neutropenia (49%/24%; febrile neutropenia, 4%/0% in arms A/B), diarrhoea (arm A, 12% and arm B, 0%), and nausea/vomiting (8%/4%). No toxic deaths occurred.
  
  
  CONCLUSIONS
  The FIRGEM strategy appears to be effective and feasible in patients with metastatic pancreatic cancer.
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Trouilloud
authors.affiliation: CHU Jean Minjoz, Besançon, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Dupont-Gossard
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.affiliation: Hôpital Privé Jean Mermoz, Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Artru
authors.affiliation: Centre Georges-François Leclerc, Dijon, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Gauthier
authors.affiliation: CHU de Tours-Hôpital Trousseau, Chambray-Les-Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lecomte
authors.affiliation: CHU Avicenne, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Aparicio
authors.affiliation: CHU Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thirot-Bidault
authors.affiliation: CHU Bichat-Claude Bernard, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lobry
authors.affiliation: CHU Antoine Béclère, Clamart, France.
authors.forename: Amani
authors.initials: A
authors.lastname: Asnacios
authors.affiliation: Centre Hospitalier René Dubos, Cergy-Pontoise, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Manet-Lacombe
authors.affiliation: CHU Jean Minjoz, Besançon, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Fein
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dubreuil
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Landi
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Zaanan
authors.affiliation: CHU Jean Minjoz, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France. Electronic address: julien.taieb@egp.aphp.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Taïeb
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine
keywords: FOLFIRI.3; Pancreatic cancer; Sequential chemotherapy