Fexapotide Triflutate Induces Selective Prostate Glandular Pharmaco-Ablation in the Rat
Authors Averback P, Gohal R, Fuska M, Prins K, Wang P
Received 17 September 2019
Accepted for publication 11 December 2019
Published 20 December 2019 Volume 2019:11 Pages 343—350
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Jan Colli
Paul Averback, Rajna Gohal, Marta Fuska, Kathleen Prins, Ping Wang
Nymox Corporation, Montreal, QC, Canada
Correspondence: Paul Averback
Nymox Corporation, 9900 Cavendish Blvd, Suite 206, St. Laurent, QC H4M 2V2, Canada
Tel +1 514 332 3222
Fax +1 514 332 2227
Introduction: A clinical challenge for interventional prostate treatments for localized prostate cancer has been to elicit cancer tissue eradication which can avoid undesirable toxicities and irreparable damage to adjacent structures. Fexapotide triflutate (FT) has been shown in human clinical trials to be a well-tolerated pharmaco-ablative agent with therapeutic benefit in patients with prostate enlargement and low-grade prostate cancer.
Methods: Studies were undertaken in vitro and in the normal male rat to characterize and quantify selective ablation of prostate glandular cells exposed to fexapotide triflutate (FT) injections. N=371 2-month-old Sprague Dawley rats received direct intraprostatic injections under ether anesthesia with laparotomy (n=268 given 0.3 mL FT 0.1–2.0 mg/mL at varied schedules, and n=103 controls), and were sacrificed at intervals of 24 hr-12 months, with measurements of prostate volume, assessments of apoptosis, prostatic nerve structures, connective tissue stroma, and vasculature. In vitro prostate cell lines treated with FT were studied by electron microscopy and RNA quantification.
Results: Evidence shows that FT leads to prostate glandular cell loss not found in controls, by apoptosis within 24–72 hrs that is highly selective for achieving near-total loss of glandular epithelium at 6 to 12 months, without any adverse microscopic effects to adjacent periprostatic nerves, vascular elements, and stroma.
Conclusion: Histological studies in the rat demonstrate that FT ablative effect is selective for prostate glandular epithelium, sparing adjacent tissues and structures in the prostate including nerves, vasculature, and stroma.
Keywords: ablation, hyperplasia, cancer, BPH, urology
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]