Oncotarget

Research Papers:

Randomized, double-blind trial of F14512, a polyamine-vectorized anticancer drug, compared with etoposide phosphate, in dogs with naturally occurring lymphoma

Pierre Boyé _, Franck Floch, François Serres, Zacharie Segaoula, Juliette Hordeaux, Quentin Pascal, Virginie Coste, Sandy Courapied, Emmanuel Bouchaert, Agata Rybicka, Claire Mazuy, Laurent Marescaux, Kévyn Geeraert, Corinne Fournel-Fleury, Alain Duhamel, François Machuron, Pierre Ferré, Aurélie Pétain, Nicolas Guilbaud, Dominique Tierny and Bruno Gomes

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Abstract

Pierre Boyé1,2,7, Franck Floch2, François Serres1,2, Zacharie Segaoula1,3, Juliette Hordeaux1, Quentin Pascal1, Virginie Coste1, Sandy Courapied1, Emmanuel Bouchaert1, Agata Rybicka1, Claire Mazuy1, Laurent Marescaux2, Kévyn Geeraert2, Corinne Fournel-Fleury4, Alain Duhamel5, François Machuron5, Pierre Ferré6, Aurélie Pétain6, Nicolas Guilbaud6, Dominique Tierny1,2 and Bruno Gomes6,8

1 OCR (Oncovet-Clinical-Research), Loos, France

2 Oncovet, Villeneuve d’Ascq, France

3 Université de Lille, JPARC - Centre de Recherche Jean-Pierre Aubert, Neurosciences et Cancer, Lille, France

4 Laboratoire Fleury-Fournel ALVEDIA, Limonest, France

5 Université Lille, Santé Publique: Epidémiologie et Qualité des Soins, Lille, France

6 Institut de Recherche Pierre Fabre, Toulouse, France

7 Current address: Department of Small Animal Teaching Hospital, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, UK

8 Current address: Hoffmann-La Roche, Switzerland

Correspondence to:

Pierre Boyé,email: pierre_boye@hotmail.fr

Keywords: etoposide phosphate; F14512; non-Hodgkin lymphoma; pet dog model; P-glycoprotein

Received: November 19, 2019     Accepted: January 13, 2020     Published: February 18, 2020

ABSTRACT

Purpose: F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas.

Experimental Design: Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 versus etoposide phosphate. Endpoints included safety and therapeutic efficacy.

Results: Twenty-five dogs were randomized to receive F14512 and 23 dogs to receive etoposide phosphate. All adverse events (AEs) were reversible, and no treatment-related death was reported. Hematologic AEs were more severe with F14512 and gastrointestinal AEs were more frequent with etoposide phosphate. F14512 exhibited similar response rate and progression-free survival (PFS) as etoposide phosphate in the global treated population. Subgroup analysis of dogs with Pgp-overexpressing NHL showed a significant improvement in PFS in dogs treated with F14512 compared with etoposide phosphate.

Conclusion: F14512 showed strong therapeutic efficacy against spontaneous NHL and exhibited a clinical benefice in Pgp-overexpressing lymphoma superior to etoposide phosphate. The results clearly justify the evaluation of F14512 in human clinical trials.


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