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

Abstract

Copyright: Boyé et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTPurpose: 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 highgrade 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.

Prognostic value of pretreatment plasma D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma

“…This study was part of a comparative oncology project assessing a new polyamine‐vectorized anticancer drug (F14512) compared with the parent drug etoposide, in dogs with naturally occurring NHL 47 . The study design was prospective, randomized and double‐blinded.…”

“…All dogs were staged based on the modified WHO five‐stage criteria for canine lymphoma as previously described 47 . Initial staging tests included a complete blood count, blood smear evaluation, biochemistry panel, ionized calcemia, whole‐body computed tomography, fine‐needle aspirates (FNA) and biopsies of peripheral lymph nodes, ultrasound‐guided liver and spleen FNA, urine analysis and bone marrow aspirates.…”

“…The treatment protocol used in this study has been previously described 47 . The same induction chemotherapy protocol was followed in all dogs over a period of 8 weeks.…”

Spermine-Conjugated Short Proline-Rich Lipopeptides as Broad-Spectrum Intracellular Targeting Antibacterial Agents

“…In this context, it is to be mentioned that spermine has also been utilized as a vector molecule for increasing the cellular uptake of the anticancer agent with clinical success. 32 Moreover, spermine, being a nonamino acid entity, could contribute to the proteolytic stability of the peptidomimetics. Previously, we also reported spermineconjugated novel antimicrobial peptidomimetics having tryptophan and phenylalanine residues in their templates for targeting the cell membrane of MRSA.…”

Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma

“…Research in comparative oncology has demonstrated that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and characterization of new therapies [1][2][3][4]. Osteosarcoma is the most common primary bone tumor reported in both human and companion dog populations [5,6].…”