***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive and rogen-independent prostate cancer . We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic , hormone-independent prostate cancer . METHODS We r and omly assigned 770 men to one of two treatments , each given in 21-day cycles : 280 mg of estramustine three times daily on days 1 through 5 , 60 mg of docetaxel per square meter of body-surface area on day 2 , and 60 mg of dexamethasone in three divided doses before docetaxel , or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily . The primary end point was overall survival ; secondary end points were progression-free survival , objective response rates , and post-treatment declines of at least 50 percent in serum prostate-specific antigen ( PSA ) levels . RESULTS Of 674 eligible patients , 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone . In an intention-to-treat analysis , the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone ( 17.5 months vs. 15.6 months , P=0.02 by the log-rank test ) , and the corresponding hazard ratio for death was 0.80 ( 95 percent confidence interval , 0.67 to 0.97 ) . The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone ( P<0.001 by the log-rank test ) . PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients , respectively ( P<0.001 ) , and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease , respectively ( P=0.30 ) . Grade 3 or 4 neutropenic fevers ( P=0.01 ) , nausea and vomiting ( P<0.001 ) , and cardiovascular events ( P=0.001 ) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone .  Pain relief was similar in both groups . CONCLUSIONS The improvement in median survival of nearly two months with docetaxel and estramustine , as compared with mitoxantrone and prednisone , provides support for this approach in men with metastatic , and rogen-independent prostate cancer BACKGROUND Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer ( mCRPC ) .  Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study . In vitro studies indicate that taxanes may act by disrupting and rogen receptor signalling . We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy . PATIENTS AND METHODS We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone , using Prostate Cancer Working Group and radiological criteria . RESULTS Of the 54 patients treated with abiraterone  , 35 subsequently received docetaxel . Docetaxel result ed in a prostate-specific antigen ( PSA ) decline of ≥50 % in nine patients [ 26 % , 95 % confidence interval ( CI ) 13 % to 43 % ] , with a median time to PSA progression of 4.6 months ( 95 % CI 4.2 % to 5.9 % ) . PSA declines ≥30 % were achieved by 13 patients ( 37 % , 95 % CI 22 % to 55 % ) . The median overall survival was 12.5 months ( 95 % CI 10.6 - 19.4 ) . All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory ( N = 8) . In the 24 patients with radiologically evaluable disease , partial responses were reported in four patients ( 11 % ) , none of whom were abiraterone-refractory . CONCLUSION The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients Purpose : To determine the clinical , pathologic , and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer . Experimental Design : Patients with biopsy Gleason scores of 8 to 10 , serum prostate-specific antigen levels > 20 ng/mL , and /or clinical stage T3 disease received weekly docetaxel ( 36 mg/m2 ) for 6 months , followed by radical prostatectomy , and were monitored with weekly visits , serum prostate-specific antigen measurements , and endorectal magnetic resonance imaging ( MRI ) . Frozen tumor specimens were collected for microarray analysis . Results : The 19 patients enrolled received 82 % of the planned chemotherapy .  Toxicity was mild to moderate ; fatigue and taste disturbance were common . Prostate-specific antigen declines of > 50 % were seen in 11 of 19 patients ( 58 % ; 95 % confidence interval , 33 - 80 % ) and endorectal MRI showed maximum tumor volume reduction of at least 25 % in 13 of 19 patients ( 68 % ; 95 % confidence interval , 47 - 85 % ) and at least 50 % in 4 patients ( 21 % ; 95 % confidence interval , 6 - 46 % ) . Sixteen patients completed chemotherapy and had radical prostatectomy ; none achieved pathologic complete response . Microarray analysis identified coordinate up-regulation of genes involved in and rogen metabolism associated with docetaxel therapy . Specifically , RNA expression for genes that decrease cellular levels of bioactive and rogens was coordinately increased in response to chemotherapy . Conclusions : Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible , well tolerated , and often results in prostate-specific antigen declines of > 50 % and decreased tumor volume on endorectal MRI . No pathologic complete responses were observed . Altered and rogen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily  and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone PURPOSE The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate , an oral , specific , irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer ( CRPC ) . PATIENTS AND METHODS In this multicenter , two-stage , phase II study , abiraterone acetate 1,000 mg was administered once daily continuously . The primary end point was achievement of a prostate-specific antigen ( PSA ) decline of > or = 50 % in at least seven of 35 patients . Per an attained phase II design , more than 35 patients could be enrolled if the primary end point was met . Secondary objectives included : PSA declines of > or = 30 % and > or = 90 % ; rate of RECIST ( Response Evaluation Criteria in Solid Tumors ) responses and duration on study ; time to PSA progression ; safety and tolerability ; and circulating tumor cell ( CTC ) enumeration . RESULTS Docetaxel-treated patients with CRPC ( N = 47 ) were enrolled .  PSA declines of > or = 30 % , > or = 50 % and > or = 90 % were seen in 68 % ( 32 of 47 ) , 51 % ( 24 of 47 ) , and 15 % ( seven of 47 ) of patients , respectively . Partial responses ( by RECIST ) were reported in eight ( 27 % ) of 30 patients with measurable disease . Median time to PSA progression was 169 days ( 95 % CI 
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EVIDENCE SYNTHESIS Taxanes are shown to interact with and rogen signalling in PCa cells at both the cytoplasmic level ( via microtubules ) and the nuclear level , affecting transcriptional regulators of and rogen-responsive gene expression .
Data from clinical trials suggest that and rogen deprivation can potentially decrease the efficacy of taxanes in treating PCa .