Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2020; 12(3): 332-346
Published online Mar 15, 2020. doi: 10.4251/wjgo.v12.i3.332
FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study
Angélique Vienot, Hortense Chevalier, Clément Bolognini, Elisabeta Gherga, Elodie Klajer, Aurélia Meurisse, Marine Jary, Stefano Kim, Christelle d’Engremont, Thierry Nguyen, Fabien Calcagno, Hamadi Almotlak, Francine Fein, Meher Nasri, Syrine Abdeljaoued, Anthony Turpin, Christophe Borg, Dewi Vernerey
Angélique Vienot, Clément Bolognini, Elodie Klajer, Marine Jary, Stefano Kim, Thierry Nguyen, Fabien Calcagno, Hamadi Almotlak, Christophe Borg, Department of Medical Oncology, Besançon University Hospital, Besançon F-25030, France
Angélique Vienot, Aurélia Meurisse, Marine Jary, Stefano Kim, Syrine Abdeljaoued, Christophe Borg, Dewi Vernerey, University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon F-25000, France
Angélique Vienot, Marine Jary, Stefano Kim, Christophe Borg, INSERM CIC-1431, Clinical Investigation Center in Biotherapy, Besançon University Hospital, Besançon F-25030, France
Hortense Chevalier, Anthony Turpin, Department of Medical Oncology, Lille University Hospital, Lille F-59000, France
Elisabeta Gherga, Meher Nasri, Department of Medical Oncology, Nord Franche-Comté Hospital, Montbéliard F-25020, France
Aurélia Meurisse, Dewi Vernerey, Methodological and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon F-25030, France
Christelle d’Engremont, Francine Fein, Department of Gastroenterology, Besançon University Hospital, Besançon F-25030, France
Author contributions: Vienot A, Borg C, Vernerey D contributed to conception and design; Vienot A, Chevalier H, Bolognini C, Gherga E, Klajer E, Jary M, Kim S, d’Engremont C, Nguyen T, Calcagno F, Almotlak H, Fein F, Nasri M, Turpin A, Borg C contributed to collection and assembly of data. Vienot A, Meurisse A, Vernerey D contributed to statistical analyses. Vienot A, Chevalier H, Turpin A, Borg C, Vernerey D contributed to data interpretation. Vienot A, Chevalier H, Abdeljaoued S, Turpin A, Borg C, Vernerey D contributed to manuscript writing; all authors read and approved the final manuscript.
Institutional review board statement: This project was approved by the National French Commission for bioinformatics data and patient liberty (CNIL; No. of CNIL declaration: 1906173 v 0).
Informed consent statement: A written informed consent form was provided by all patients.
Conflict-of-interest statement: No author has any conflict of interest.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Angélique Vienot, MD, Department of Medical Oncology, Besançon University Hospital, 3 Boulevard Alexandre Fleming, Besançon F-25030, France. angelique.vienot@inserm.fr
Received: August 24, 2019
Peer-review started: August 24, 2019
First decision: October 18, 2019
Revised: December 26, 2019
Accepted: January 14, 2020
Article in press: January 14, 2020
Published online: March 15, 2020
Abstract
BACKGROUND

FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer.

AIM

To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.

METHODS

Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI (n = 165) or FOLFIRINOX (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared.

RESULTS

Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; P = 0.219) and progression-free survival (hazard ratio = 1.27; P = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group vs 47.8% in the FOLFIRINOX group (P = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort vs 19.5% in the FOLFIRINOX cohort (P = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens.

CONCLUSION

FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Keywords: Advanced pancreatic cancer, First-line chemotherapy, FOLFOXIRI, FOLFIRINOX, Propensity score, Cohort study

Core tip: This is the first study to compare FOLFOXIRI and FOLFIRINOX regimens head-to-head, to assess whether FOLFOXIRI contributes to a better balance in the toxicity/efficacy ratio in advanced pancreatic ductal adenocarcinoma. These findings do not suggest any therapeutic benefit of FOLFOXIRI compared to FOLFIRINOX in first-line chemotherapy. These results show that additional evaluation is not warranted in future clinical trials. FOLFIRINOX chemotherapy remains the standard of care first-line therapy in metastatic pancreatic ductal adenocarcinoma. Interestingly, the low hematological toxicity rates in both regimens underscore the relevance of prophylactic administration of hematopoietic growth factors in routine use after each polychemotherapy cycle.