***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 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 63 Background : In two r and omized trials a survival benefit has been shown for docetaxel ( T ) in metastatic , hormone refractory prostate cancer PrCa ) . In order to increase the recurrence-free survival and overall survival with adjuvant treatment we conducted a r and omized trial using T in patients ( pts ) with high risk PrCa after radical radiotherapy ( RT ) .  METHODS Between May 2007 and April 2009 100 pts with PrCa Gleason score ( GS ) 7 ( 4 + 3 ) and cT2 tumors with PSA > 10 to < 70 ng/mL or cT2 tumors with GS 8 - 10 or any cT3 tumors without metastases were r and omized between surveillance ( S ) or six courses of T 75 mg/m2 q21d at the end of RT . Neoadjuvant + adjuvant LHRH-treatment for 9 mo was m and atory . The defined end-point is PSA relapse ( ASTRO-RTOG guidelines ) . The groups were well balanced ; mean age 65 vs 66 years , ECOG ( 0/1 , % ) 90/10 vs 90/10 ; time from diagnosis 262 vs 270 days , GS ( 6 - 7/8 - 10 , % ) 60/40 vs 44/56 ; tumor stage ( T2/T3 , % ) 26/74 vs 28/72 in groups T vs S , respectively . The mean PSA of the 100 pts at the time of diagnosis was 21.9 ng/mL and the nadir PSA after RT was 0.25 ng/mL. By September 2010 227 out of 378 pts have been r and omized to this SPCG 13 trial , NTC 006653848 . RESULTS During T treatment Grade ( G ) 3 adverse event ( AEs ) occurred in 15 pts ( 30 % ) and G 4 AEs in 30 pts ( 60 % ) mainly due to bone marrow toxicity , which was higher than expected ; neutropenia G 3 - 4 in 72 % of the pts . Febrile neutropenia in 24 % of the pts , neutropenic infection in 10 % the pts and G3 infection without neutropenia in 4 % of pts was recorded . Nonhematological G 3 AEs ( pts ) were rare ; anorexia ( 1 ) , diarrhea ( 3 ) , fatigue ( 5 ) , mucositis ( 1 ) , nausea ( 1 ) and pain ( 1 ) . Other severe SAEs related to T were pulmonary embolism and renal failure . However , only three pts stopped T before 6 cycles were completed due to toxicity . No deaths have occurred . In the S arm only one patient experienced G 3 toxicity ( pain ) 12 weeks after the r and omization . CONCLUSIONS Adjuvant T chemotherapy after RT has a higher frequency of neutropenia than previous studies on pts with metastatic disease , but very similar to the SPCG 12 trial of adjuvant T after surgery . Otherwise the treatment was quite well tolerated . [ Table : see text ] 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 Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer . To assess the effect of radiotherapy , we did an open phase III study comparing endocrine therapy with and without local radiotherapy , followed by castration on progression . METHODS This r and omised trial included men from 47 centres in Norway , Sweden , and Denmark . Between February , 1996 , and December , 2002 , 875 patients with locally advanced prostate cancer ( T3 ; 78 % ; PSA<70 ; N0 ; M0 ) were central ly r and omly assigned by computer to endocrine treatment alone ( 3 months of total and rogen blockade followed by continuous endocrine treatment using flutamide ; 439 patients ) , or to the same endocrine treatment combined with radiotherapy ( 436 patients ) . The primary endpoint was prostate-cancer-specific survival , and analysis was by intention to treat . This study is registered as an international st and ard r and omised controlled trial , number IS RCT N01534787 . FINDINGS After a median follow-up of 7.6 years , 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer . The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9 % in the endocrine alone group and 11.9 % in the endocrine plus radiotherapy group ( difference 12.0 % , 95 % CI 4.9 - 19.1 % ) , for a relative risk of 0.44 ( 0.30 - 0.66 ) . At 10 years , the cumulative incidence for overall mortality was 39.4 % in the endocrine alone group and 29.6 % in the endocrine plus radiotherapy group ( difference 9.8 % , 0.8 - 18.8 % ) , for a relative risk of 0.68 ( 0.52 - 0.89 ) . Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group ( 74.7%vs 25.9 % , p<0.0001 ; HR 0.16 ; 0.12 - 0.20 ) . After 5 years , urinary , rectal , and sexual problems were slightly more frequent in the endocrine plus radiotherapy group . INTERPRETATION In patients with locally advanced or high-risk local prostate cancer , addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality , and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone . In the light of these data , endocrine treatment plus radiotherapy should be the new st and ard Purpose We have previously reported that radiotherapy ( RT ) added to and rogen-deprivation therapy ( ADT ) improves survival in men with locally advanced prostate cancer . Here , we report the prespecified final analysis of this r and omized trial . Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94 - 0110 was a r and omized controlled trial of patients with locally advanced prostate cancer . Patients with T3 - 4 , N0/Nx , M0 prostate cancer or T1 - 2 disease with either prostate-specific antigen ( PSA ) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were r and omly assigned to lifelong ADT alone or to ADT+RT . The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone . Overall survival was compared using a log-rank test stratified for prespecified variables . Results One thous and two hundred five patients were r and omly assigned between 1995 and 2005 , 602 to ADT alone and 603 to ADT+RT . At a median follow-up time of 8 years , 465 patients had died , including 199 patients from prostate cancer . Overall survival was significantly improved in the patients allocated to ADT+RT ( hazard ratio [ HR ] , 0.70 ; 95 % CI , 0.57 to 0.85 ; P < .001 ) . Deaths from prostate cancer were significantly reduced by the addition of RT to ADT ( HR , 0.46 ; 95 % CI , 0.34 to 0.61 ; P < .001 ) . Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity , but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT . Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer To report a r and omized , placebo‐controlled study of treatment with zoledronic acid every 3 months in patients with hormone‐sensitive prostate cancer , both with and without bone metastases , to assess the effect on bone mineral density ( BMD ) and markers of bone turnover Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy .  We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N7 
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INTERPRETATION The addition of docetaxel to st and ard of care should be considered st and ard care for men with M1 hormone-sensitive prostate cancer who are starting treatment for the first time .
No evidence exists to suggest that zoledronic acid  improves survival in men with M1 or M0 disease , and any potential benefit is probably small .