***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: PURPOSE To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a r and omized controlled trial . PATIENTS AND METHODS We r and omized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone ( 10 mg daily ) . Nonresponding patients on prednisone  could receive mitoxantrone subsequently . The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients ( or complete loss of pain if initially 1 + ) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart . Secondary end points were a decrease of > or = 50 % in use of analgesic medication without an increase in pain , duration of response , and survival . Health-related quality of life was evaluated with a series of linear analog self- assessment scales ( LASA and the Prostate Cancer-Specific Quality -of-Life Instrument [ PROSQOLI ] ) , the core question naire of the European Organization for Research and Treatment of Cancer ( EORTC ) , and a disease-specific module . RESULTS Palliative response was observed in 23 of 80 patients ( 29 % ; 95 % confidence interval , 19 % to 40 % ) who received mitoxantrone plus prednisone , and in 10 of 81 patients ( 12 % ; 95 % confidence interval , 6 % to 22 % ) who received prednisone alone ( P = .01 ) . An additional seven patients in each group reduced analgesic medication > or = 50 % without an increase in pain . The duration of palliation was longer in patients who received chemotherapy ( median , 43 and 18 weeks ; P < .0001 , log-rank ) . Eleven of 50 patients r and omized to prednisone treatment responded after addition of mitoxantrone . There was no difference in overall survival . Treatment was well tolerated , except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone . Most responding patients had an improvement in quality -of-life scales and a decrease in serum prostate-specific antigen ( PSA ) level . CONCLUSION Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer 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 Purpose : With the approval of immunotherapies for a variety of indications , methods to assess treatment benefit addressing the response patterns observed are important . We evaluated RECIST criteria –based overall response rate ( ORR ) and progression-free survival ( PFS ) as potential surrogate endpoints of overall survival ( OS ) , and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials . Experimental Design : Thirteen r and omized , multicenter , active-control trials containing immunotherapeutic agents su bmi tted to the FDA were analyzed . Associations between treatment effects of ORR , PFS , modified PFS , and OS were evaluated at individual and trial levels . Patient-level responder analysis was performed for PFS and OS . Results : The coefficient of determination ( R² ) measured the strength of associations , where values near 1 imply surrogacy and values close to 0 suggest no association . At the trial level , the association between hazard ratios ( HR ) of PFS and OS was R2 = 0.1303 , and between the odds ratio ( OR ) of ORR and HR of OS was R2 = 0.1277 . At the individual level , the Spearman rank correlation coefficient between PFS and OS was 0.61 . Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1 , and individual-level correlations were approximately 0.6 . HRs of PFS and OS for responders versus nonresponders were 0.129 [ 95 % confidence interval ( CI ) , 0.11–0.15 ] and 0.118 ( 95 % CI , 0.11–0.13 ) , respectively . Conclusions : Although responders exhibited longer survival and PFS than nonresponders , the trial-level and individual-level associations were weak between PFS/ORR and OS . Modifications to PFS did not improve associations . Clin Cancer Res ; 24(10 ) ; 2268–75 . © 2018 AACR . See related commentary by Korn and Freidlin , p. PURPOSE To evaluate the efficacy and safety of atrasentan ( ABT-627 ) , an endothelin-A receptor antagonist , in the treatment of asymptomatic , hormone-refractory prostatic adenocarcinoma . PATIENTS AND METHODS A double-blind , r and omized , placebo-controlled clinical trial of hormone-refractory prostate cancer ( HRPCa ) patients was conducted in the United States and Europe . Two hundred eighty-eight asymptomatic patients with HRPCa and evidence of metastatic disease were r and omly assigned to one of three study groups receiving a once-daily oral dose of placebo , 2.5 mg atrasentan , or 10 mg atrasentan , respectively . Primary end point was time to progression ; secondary end points included time to prostate-specific antigen ( PSA ) progression , bone scan changes , and changes in bone and tumor markers . RESULTS The three treatment groups were similar in all baseline characteristics . Median time to progression in intent-to-treat ( ITT ) patients ( n = 288 ) was longer in the 10-mg atrasentan group compared with the placebo group : 183 v 137 days , respectively ; ( P = .13 ) . Median time to progression in evaluable patients ( n = 244 ) was significantly prolonged , from 129 days ( placebo group ) to 196 days ( 10-mg atrasentan group ; P = .021 ) . For both ITT and evaluable population s in the 10-mg atrasentan group , median time to PSA progression was twice that of the placebo group ( 155 v 71 days ; P = .002 ) . Patients who received placebo continued to have significant increases from baseline in serum ( lactate dehydrogenase [ LDH ] ) , a marker of disease burden ; elevations in LDH were uniformly attenuated by atrasentan in the ITT population . Headache , peripheral edema , and rhinitis were primary side effects , typically of mild to moderate severity . Quality of life was not adversely affected by atrasentan . CONCLUSION Atrasentan is an oral , targeted therapy with favorable tolerability and the potential to delay progression of HRPCa BACKGROUND The alpha-emitter radium-223 ( (223)Ra ) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer . We aim ed to study mature outcomes from a r and omised , multicentre , phase II study of (223)Ra . METHODS Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy  were assigned to four intravenous injections of (223)Ra ( 50 kBq/kg , 33 patients ) or placebo ( 31 patients ) , given every 4 weeks . Primary endpoints were change in bone-alkaline phosphatase ( ALP ) concentration and time to skeletal-related events ( SREs ) . Secondary endpoints included toxic effects , time to prostate-specific-antigen ( PSA ) progression , and overall survival . All tests were done at a 5 % significance level , based on intention to treat . FINDINGS Median relative change in bone-ALP during treatment was -65.6 % ( 95 % CI -69.5 to -57.7 ) and 9.3 % ( 3.8 - 60.9 ) in the (223)Ra group and placebo groups , respectively ( p<0.0001 , Wil 
    Output:
    
Measurable tumor responses in phase 2 trials were higher for successful therapies in phase 3 trials in chemotherapy-naive men with mCRPC , but were less correlated with success in trials investigating docetaxel combination regimens or the post chemotherapy mCRPC setting .
Many failed agents did not produce higher than expected response rates over control arms ; however , several agents such as anti-angiogenic therapies or orteronel produced higher than expected responses without survival benefit .
Conclusions Objective responses in men with mCRPC may be associated with prolonged survival , but this association is mechanism dependent and inconsistent across trials or disease states .