LHRH antagonists decrease testosterone without any testosterone surge , and they may be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
LHRH antagonists decrease testosterone without any testosterone surge , and they might be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
OBJECTIVE To present a summary of the 2013 version of the European Association of Urology ( EAU ) guidelines on the treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
The guidelines were up date d , and levels of evidence and /or grade s of recommendation were added to the text based on a systematic review of the literature that included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Treatment of CRPC includes sipuleucel-T , abiraterone acetate plus prednisone ( AA/P ) , or chemotherapy with docetaxel at 75mg/m(2 ) every 3 wk .
Cabazitaxel , AA/P , enzalutamide , and radium-223 are available for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced , metastatic , and castration-resistant PCa is rapidly changing .
PATIENT SUMMARY We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Relapse after local therapy is defined by prostate-specific antigen ( PSA ) values > 0.2 ng/ml following radical prostatectomy ( RP ) and > 2 ng/ml above the nadir and after radiation therapy .
Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels < 0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures .
Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study
BACKGROUND MDV3100 is an and rogen-receptor antagonist that blocks and rogens from binding to the and rogen receptor and prevents nuclear translocation and co-activator recruitment of the lig and -receptor complex . It also induces tumour cell apoptosis , and has no agonist activity . Because growth of castration-resistant prostate cancer is dependent on continued and rogen-receptor signalling , we assessed the antitumour activity and safety of MDV3100 in men with this disease . METHODS This phase 1 - 2 study was undertaken in five US centres in 140 patients . Patients with progressive , metastatic , castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg . The final daily doses studied were 30 mg ( n=3 ) , 60 mg ( 27 ) , 150 mg ( 28 ) , 240 mg ( 29 ) , 360 mg ( 28 ) , 480 mg ( 22 ) , and 600 mg ( 3 ) . The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose . The trial is registered with Clinical Trials.gov , number NCT00510718 . FINDINGS We noted antitumour effects at all doses , including decreases in serum prostate-specific antigen of 50 % or more in 78 ( 56 % ) patients , responses in soft tissue in 13 ( 22 % ) of 59 patients , stabilised bone disease in 61 ( 56 % ) of 109 patients , and conversion from unfavourable to favourable circulating tumour cell counts in 25 ( 49 % ) of the 51 patients . PET imaging of 22 patients to assess and rogen-receptor blockade showed decreased (18)F-fluoro-5alpha-dihydrotestosterone binding at doses from 60 mg to 480 mg per day ( range 20 - 100 % ) . The median time to progression was 47 weeks ( 95 % CI 34-not reached ) for radiological progression . The maximum tolerated dose for sustained treatment ( > 28 days ) was 240 mg . The most common grade 3 - 4 adverse event was dose-dependent fatigue ( 16 [ 11 % ] patients ) , which generally resolved after dose reduction . INTERPRETATION We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer . The results of this phase 1 - 2 trial vali date in man pre clinical studies implicating sustained and rogen-receptor signalling as a driver in this disease . FUNDING Medivation , the Prostate Cancer Foundation , National Cancer Institute , the Howard Hughes Medical Institute , Doris Duke Charitable Foundation , and Department of Defense Prostate Cancer Clinical Trials Consortium
LHRH antagonists decrease testosterone without any testosterone surge , and they may be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
LHRH antagonists decrease testosterone without any testosterone surge , and they might be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
OBJECTIVE To present a summary of the 2013 version of the European Association of Urology ( EAU ) guidelines on the treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
The guidelines were up date d , and levels of evidence and /or grade s of recommendation were added to the text based on a systematic review of the literature that included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Treatment of CRPC includes sipuleucel-T , abiraterone acetate plus prednisone ( AA/P ) , or chemotherapy with docetaxel at 75mg/m(2 ) every 3 wk .
Cabazitaxel , AA/P , enzalutamide , and radium-223 are available for second-line treatment of CRPC following docetaxel .
CONCLUSIONS The knowledge in the field of advanced , metastatic , and castration-resistant PCa is rapidly changing .
PATIENT SUMMARY We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) .
Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) .
Relapse after local therapy is defined by prostate-specific antigen ( PSA ) values > 0.2 ng/ml following radical prostatectomy ( RP ) and > 2 ng/ml above the nadir and after radiation therapy .
Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels < 0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures .