***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 Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving and rogen-deprivation therapy .  Replacing and rogens before progression of the disease is hypothesized to prolong and rogen dependence . METHODS Men with newly diagnosed , metastatic , hormone-sensitive prostate cancer , a performance status of 0 to 2 , and a prostate-specific antigen ( PSA ) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an anti and rogen agent for 7 months . We then r and omly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent and rogen deprivation  , with patients stratified according to prior or no prior hormonal therapy , performance status , and extent of disease ( minimal or extensive ) . The co primary objectives were to assess whether intermittent  therapy  was noninferior to continuous therapy with respect to survival , with a one-sided test with an upper boundary of the hazard ratio of 1.20 , and whether quality of life differed between the groups 3 months after r and omization . RESULTS A total of 3040 patients were enrolled , of whom 1535 were included in the analysis : 765 r and omly assigned to continuous and rogen deprivation and 770 assigned to intermittent and rogen deprivation . The median follow-up period was 9.8 years . Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group ( hazard ratio for death with intermittent therapy , 1.10 ; 90 % confidence interval , 0.99 to 1.23 ) . Intermittent therapy was associated with better erectile function and mental health ( P<0.001 and P=0.003 , respectively ) at month 3 but not thereafter . There were no significant differences between the groups in the number of treatment-related high- grade adverse events . CONCLUSIONS Our findings were statistically inconclusive . In patients with metastatic hormone-sensitive prostate cancer , the confidence interval for survival exceeded the upper boundary for noninferiority , suggesting that we can not rule out a 20 % greater risk of death with intermittent therapy than with continuous therapy , but too few events occurred to rule out significant inferiority of intermittent therapy . Intermittent therapy result ed in small improvements in quality of life . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00002651 . ) Objective To assess the role of mitozantrone , active in relapsed prostate cancer , as an adjuvant to hormonal treatment in patients with advanced prostate cancer 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 We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine , given in addition to st and ard and rogen deprivation , would delay the appearance of castrate-resistant disease . PATIENTS AND METHODS Eligible patients had metastatic prostate cancer threatening enough to justify sustained and rogen ablation and were fit enough for chemotherapy . The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen , new radiographic lesions , worsening cancer-related symptoms , or receipt of any other systemic therapy . RESULTS Three hundred six patients were registered ; 286 are reported .  Median time to progression was 24 months ( 95 % CI , 18 to 39 months ) in the st and ard therapy arm , and 35 months ( 95 % CI , 26 to 44 months ) in the chemohormonal group ( P = .39 ) . At median follow-up of 6.4 years , overall survival was 5.4 years ( 95 % CI , 4.7 to 7.8 years ) in the st and ard therapy arm versus 6.1 years ( 95 % CI , 5.1 to 10.1 years ; P = .41 ) . Prostate-specific antigen kinetics at the time of and rogen ablation and the nadir after hormone treatment were strongly correlated with survival . Chemotherapy significantly increased the burden of therapy , with 51 % of patients experiencing an adverse event of grade 3 or worse , especially thromboembolic events . CONCLUSION There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype BACKGROUND Early risk-stratified chemotherapy is a st and ard treatment for breast , colorectal , and lung cancers , but not for high-risk localised prostate cancer . Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer . We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer . METHODS We did this r and omised phase 3 trial at 26 hospitals in France . We enrolled patients with treatment-naive prostate cancer and at least one risk factor ( ie , stage T3-T4 disease , Gleason score of ≥8 , prostate-specific antigen concentration > 20 ng/mL , or pathological node-positive ) . All patients underwent a staging pelvic lymph node dissection . Patients were r and omly assigned ( 1:1 ) to either and rogen deprivation therapy ( ADT ; goserelin 1 
    Output:
    
This meta- analysis shows a significant OS benefit from concomitant administration of docetaxel and ADT in patients with metastatic hormone-sensitive PCa .