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.
Highlights
Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies [1,2,3]
Hematologic adverse events (AEs) were more severe with F14512 and gastrointestinal AEs were more frequent with etoposide phosphate
Subgroup analysis of dogs with Pgp-overexpressing non-Hodgkin lymphoma (NHL) showed a significant improvement in progression-free survival (PFS) in dogs treated with F14512 compared with etoposide phosphate
Summary
Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies [1,2,3]. Canine NHL share many biological and therapeutic similarities with their human counterparts, including clinical presentation, biological behavior, and therapeutic responses [4,5,6]. These similarities support the use of the canine model as a comparative, relevant large animal model to study new therapies for both human and canine benefit. The most common mechanism of MDR is the overexpression of ATP binding cassette (ABC) transporters, which actively pump numerous chemotherapeutic drugs outside the cancer cells, attenuating drug efficacy and resulting in resistance to treatment [10,11,12]. The ABC transporter subfamily B member 1 (ABCB1/MDR1, P-glycoprotein, Pgp) is one of the most important transporters to confer MDR to cancer cells [13,14,15,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
