613 IMMEDIATE, COMPARED TO DEFERRED, COMBINED ANDROGEN BLOCKADE PROLONGS TIME TO CASTRATE-RESISTANT LNCAP PROSTATE CANCER PROGRESSION IN VIVO

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011613 IMMEDIATE, COMPARED TO DEFERRED, COMBINED ANDROGEN BLOCKADE PROLONGS TIME TO CASTRATE-RESISTANT LNCAP PROSTATE CANCER PROGRESSION IN VIVO Hidetoshi Kuruma, Kilian Gust, Hiroaki Matsumoto, Amina Zoubeidi, Chirstian Thomas, Francois Lamoureux, and Martin Gleave Hidetoshi KurumaHidetoshi Kuruma Vancouver, Canada More articles by this author , Kilian GustKilian Gust Vancouver, Canada More articles by this author , Hiroaki MatsumotoHiroaki Matsumoto Vancouver, Canada More articles by this author , Amina ZoubeidiAmina Zoubeidi Vancouver, Canada More articles by this author , Chirstian ThomasChirstian Thomas Vancouver, Canada More articles by this author , Francois LamoureuxFrancois Lamoureux Vancouver, Canada More articles by this author , and Martin GleaveMartin Gleave Vancouver, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1466AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy is standard for advanced prostate cancer (PCa). Combined androgen blockade (CAB) refers to surgical or medical castration plus an anti-androgen is considered maximum androgen blockade therapy. However, there is no consensus about optimal timing of anti-androgen induction after castration. In this study, we compared effects of immediate vs. delayed administration of bicalutamide after castration on time to castrate-resistant LNCaP tumor growth. METHODS Androgen dependent human prostate cancer LNCaP cells were inoculated into male athymic nude mice subcutaneously. Serum PSA level and tumour volumes were followed weekly. When serum PSA values reached 50ng/ml, mice were castrated and divided into 3 groups including immediate CAB, CAB after progression to castration resistance (deferred CAB), or vehicle-only dosing. 50mg/kg of bicalutamide was used as an anti- androgen. RESULTS Forty one mice entered this study. Averages of PSA and tumour volume were similar prior to castration in all three groups. In the immediate CAB group, PSA declined to −91.2% from baseline 2 weeks after CAB, compared to −64.6% for vehicle. In the deferred CAB group, PSA declined −50.4% by 1W after castration, and returned to pre-castration levels at 4 weeks. By 12 weeks post-castration, PSA levels were −29.0%, +197.0% and +118.1% from baseline for the immediate CAB, deferred CAB and vehicle groups, respectively. PSA levels in the immediate CAB group were significantly lower than deferred CAB (p=0.04 at 12 weeks). Tumor volume in the immediate CAB group decreased −10.2% at 2 weeks after CAB, while tumor volume in the deferred CAB and vehicle-only groups continued to increase post-castration. By 12 weeks after castration, tumor volume increased by +98.2%, +307.4% and +546.9% from base line for immediate CAB, deferred CAB and vehicle groups, respectively. CONCLUSIONS Immediate CAB, at time of first-line castration, prolonged time to recurrence compared deferred CAB in the androgen-sensitive LNCaP models, and has ongoing implications to the clinical disease as more potent anti-androgens are under development. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e247 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidetoshi Kuruma Vancouver, Canada More articles by this author Kilian Gust Vancouver, Canada More articles by this author Hiroaki Matsumoto Vancouver, Canada More articles by this author Amina Zoubeidi Vancouver, Canada More articles by this author Chirstian Thomas Vancouver, Canada More articles by this author Francois Lamoureux Vancouver, Canada More articles by this author Martin Gleave Vancouver, Canada More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...