Mp52-02 a Novel Oral ? and ? Tubulin Inhibitor, Veru-111, Has Potent Activity Against Paclitaxel Sensitive and Resistant Prostate Cancer
Year: 2018
Type: article
Abstract: You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2018MP52-02 A NOVEL ORAL ? AND ? TUBULIN INHIBITOR, VERU-111, HAS POTENT ACTIVITY AGAINST PACLITAXEL SENSITIVE AND RESISTANT PROSTATE CANCER Robert Getzenberg, James Dalton, Duane Miller, and Mitchell Steiner Robert GetzenbergRobert Getzenberg More articles by this author , James DaltonJames Dalton More articles by this author , Duane MillerDuane Miller More articles by this author , and Mitchell SteinerMitchell Steiner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1653AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Following proven efficacy of docetaxel against hormone sensitive advanced prostate cancer (CHAARTED and STAMPEDE), the use of docetaxel for the treatment of hormone sensitive and castrate resistant metastatic prostate cancer has increased. Unfortunately, the utility of taxanes in prostate cancer has been limited because of resistance, the need for IV infusion, and the treatment toxicity. VERU-111 is a highly orally available, a and β tubulin inhibitor, developed using a rationale design strategy to bind through hydrogen bonds to the a and β subunits of tubulin. VERU-111 inhibits tubulin polymerization and is not a substrate for multi-drug resistance proteins. METHODS In this study, dosing regimens of VERU-111 (oral) were tested in comparison with docetaxel (IV) and a vehicle (oral) in PC3 as well as in paclitaxel resistant PC3 (PC3-TXR) xenograft models. VERU-111 was evaluated at 3.3 mg/kg (5 days/week), 10 mg/kg (3 days/week), 15 mg/kg (2 days per week), 15 mg/kg (3 days per week) and 20 mg/kg (1 day/week). The animals were treated for 28 days and tumor volume and percentage size were calculated. RESULTS In the parental PC-3 model, animals treated with oral VERU-111, in all of the dose schemes tested, performed statistically indistinguishably from the IV docetaxel administration. In the PC3-TXR model, IV docetaxel had no impact on tumor growth whereas oral VERU-111 resulted in almost complete inhibition of tumor growth at 3.3 mg/kg (5 days/week) and 10 mg/kg (3 days/ week) as well as 20 mg/kg (1 day/week). In early toxicity studies, the animals treated with VERU-111 did not suffer any significant safety signals and gained weight during treatment. CONCLUSIONS VERU-111 is a novel, oral a and β tubulin inhibitor that has characteristics making it an ideal candidate to be a therapeutic option for hormone sensitive and castrate resistant advanced prostate cancer. VERU-111 can be administered, with efficacy, as infrequent as once per week and will not require daily dosing. Additional toxicity studies are currently being performed with a Phase 1/2 study being planned to begin later this year. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e694 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Robert Getzenberg More articles by this author James Dalton More articles by this author Duane Miller More articles by this author Mitchell Steiner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Authors: Robert Getzenberg, James Dalton, Duane Miller, Mitchell Steiner
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2796461696