***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 . ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 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 
    Output:
    
In docetaxel-pretreated patients  enzalutamide , abiraterone-prednisone and cabazitaxel-prednisone can improve overall survival of patients , compared to placebo or to best of care at the time of study ( mitoxantrone-prednisone ) .
Agents targeting the and rogen axis ( enzalutamide , abiraterone , orteronel ) significantly prolonged rPFS , compared to placebo .