Long-Term Efficacy and Safety of Nilutamide Plus Castration in Advanced Prostate Cancer, and the Significance of Early Prostate Specific Antigen Normalization

Abstract

Please be advised that this information was generated on 2018-05-13 and may be subject to change. 0 0 2 2 -5 3 4 7 /9 7 /1 5 8 1~0 1 6 0 $ 0 3 .0 0 /0 T he J ournal o f U rology C o p y rig h t © 1997 b y A m erican U rological A^v^rv n o N , I nc. V ol. 1 5 8 , 1 6 0 -1 6 3 , J u l y l í P rin ted in U.& M aterials a n d M ethods; A large double-blind tria l w as done on 457 p atien ts random ized to receive n ilu ta m id e or placebo after orchiectomy. LONG-TERM EFFICACY AND SAFETY OF NILUTAMIDE PLUS CASTRATION IN ADVANCED PROSTATE CANCER, AND THE SIGNIFICANCE OF EARLY PROSTATE SPECIFIC ANTIGEN NORMALIZATIONGERHARDR esults: A t 8.5 y e a rs of followup significant benefits were found for progression and su rv iv al in favor of p a tie n ts receiving n ilu tam id e an d orchiectomy. In addition, norm alized p ro state specific an tig en levels a t 3 m o n th s from th e s ta r t of th e ra p y w ere predictive of good long-term outcome. M oreover, com bined an d ro g en blockade w ith nilutam ide increased th e chance of p a tie n ts h av in g n o rm al p ro sta te specific an tig en levels a t 3 m onths. N ilutam ide w as well to lerated in th e long te rm w ith no in cre ase in th e incidence of drug specific adverse events.Conclusions: W ith lo ng-term followup of p a tie n ts w ith advanced p ro state cancer, th e combi n a tio n of n ilu ta m id e a n d orchiectom y h as significant benefits in in terv al to progression an d im proved su rv iv al com pared to orchiectom y and placebo.K ey W o rd s: p ro sta tic neoplasms, orchiec

Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer

“…Agonist binding disrupts the inhibitory HSP-AR complex, exposing a nuclear localization signal in the receptor that enables nuclear translocation (49). We used high-content imaging (Cellomics ArrayScan) to evaluate the subcellular localization of the AR in an unbiased manner in AR-transfected HEK293 and VCAP cells (a) AR antagonists, flutamide (43), bicalutamide (4), and nilutamide (44), which function as partial agonists in models of CRPC (purple cluster); (b) RU486 (45) and cyproterone acetate (CPA) (46) (gray cluster); (c) enzalutamide and its structurally related analogs ARN509 and NC7 (11); and (d) seviteronel, galeterone, and abiraterone (orange cluster). Additional ligands found to cluster with the CYP17 inhibitors include D36 and D80, two noncompetitive AR antagonists that we previously reported to have efficacy in models of CRPC (47).…”

Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide

“…These results are comparable with the results reported in the literature that after the start about 75 ± 80% of the patients reach a PSA nadir below 4 ng/ml after 3 or 6 months. 13,15 In the literature only a small amount of data are available on the use of nilutamide as monotherapy. 17 In this project 80 patients (11%) received nilutamide monotherapy as indicated by the urologist.…”

Maximum androgen blockade: a case study report

“…22 The third study by the Anandron Study Group compared bilateral orchiectomy plus nilutamide with bilateral orchiectomy. 24 In all three studies, median time to progression and median time of overall survival were longer in the MAB arm (Table 2). This reached statistical signi®cance in the SWOG-INT 0036 trial.…”

“…22,24,30 The Southwest Oncology Group (SWOG-INT 0036) compared leuprolide plus¯utamide with leuprolide plus placebo. 30 The EORTC-30853 study compared goserelin acetate plus¯utamide with bilateral orchiectomy.…”