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)

Isabelle Trouilloud, Anne Claire Dupont-Gossard, David Malka, Pascal Artru, Mélanie Gauthier, Thierry Lecomte, Thomas Aparicio, Anne Thirot-Bidault, Céline Lobry, Amani Asnacios, Sophie Manet-Lacombe, Francine Fein, Olivier Dubreuil, Bruno Landi, Aziz Zaanan, Franck Bonnetain, Julien Taïeb

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31 Scopus citations

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. Conclusion The FIRGEM strategy appears to be effective and feasible in patients with metastatic pancreatic cancer.

Original languageEnglish
Pages (from-to)3116-3124
Number of pages9
JournalEuropean Journal of Cancer
Volume50
Issue number18
DOIs
StatePublished - Dec 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.

Funding

Financial support for this research was provided by Pfizer , AGEO and AROLD (Association pour la Recherche en Oncologie Digestive). We thank the patients who participated in this study, their families for their trust, all the investigators, and their supporting staff.

FundersFunder number
AGEO
Association pour la Recherche en Oncologie Digestive
Pfizer

    Keywords

    • FOLFIRI.3
    • Pancreatic cancer
    • Sequential chemotherapy

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