Titre :

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma.

Auteur(s) :

Tierny, Dominique [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Serres, François [Auteur]
Segaoula, Zacharie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Bemelmans, Ingrid [Auteur]
Bouchaert, Emmanuel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Pétain, Aurélie [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Brel, Viviane [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Couffin, Stéphane [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Marchal, Thierry [Auteur]
VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement [VAS]
Nguyen, Laurent [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Thuru, Xavier [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]

Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer
Ferré, Pierre [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Guilbaud, Nicolas [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]
Gomes, Bruno [Auteur]
Centre de Recherche Pierre Fabre [Centre de R&D Pierre Fabre]

Titre de la revue :

Clinical cancer research : an official journal of the American Association for Cancer Research

Nom court de la revue :

Clin Cancer Res

Numéro :

21

Pagination :

5314-23

Date de publication :

2015-12-01

ISSN :

1557-3265

Mot(s)-clé(s) en anglais :

Animals
Antineoplastic Agents
Biomarkers
Cell Line, Tumor
Dog Diseases
Dogs
Drug Evaluation, Preclinical
Female
Histones
Humans
Lymphoma
Male
Neoplasm Staging
Podophyllotoxin
Topoisomerase II Inhibitors
Treatment Outcome

Résumé en anglais : [en]

F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in ...
Lire la suite >F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relationship of F14512 in this indication, and potential biomarkers that could be translated into human trials. Twenty-three dogs with stage III-IV naturally occurring lymphomas were enrolled in the phase I dose-escalation trial, which consisted of three cycles of F14512 i.v. injections. Endpoints included safety and therapeutic efficacy. Serial blood samples and tumor biopsies were obtained for PK/PD and biomarker studies. Five dose levels were evaluated to determine the recommended dose. F14512 was well tolerated, with the expected dose-dependent hematologic toxicity. F14512 induced an early decrease of tumoral lymph node cells, and a high response rate of 91% (21/23) with 10 complete responses, 11 partial responses, 1 stable disease, and 1 progressive disease. Phosphorylation of histone H2AX was studied as a potential PD biomarker of F14512. This trial demonstrated that F14512 can be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy. Additional evaluation of F14512 is needed to compare its efficacy with standards of care in dogs, and to translate biomarker and efficacy findings into clinical trials in humans.Lire moins >

Audience :

Non spécifiée

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2021-03-23T12:26:02Z