***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 PURPOSE Anti and rogen withdrawal ( AAWD ) results in a prostate-specific antigen ( PSA ) response ( decline in PSA level of > or = 50 % ) in 15 % to 30 % of and rogen-independent prostate cancer ( AiPCa ) patients . Thereafter , adrenal and rogen ablation with agents such as ketoconazole ( K ) is commonly utilized . The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy . PATIENTS AND METHODS AiPCa patients were r and omized to undergo AAWD alone  ( n=132 ) , or together with K ( 400 mg orally [ p.o . ] tid ) and hydrocortisone ( 30 mg p.o . each morning , 10 mg p.o . each evening ; n=128 ) . Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS Eleven percent of patients undergoing AAWD alone had a PSA response , compared to 27 % of patients who underwent AAWD and simultaneous K ( P=.0002 ) . Objective responses were observed in 2 % of patients treated with AAWD alone compared to 20 % in patients treated with AAWD/K ( P=.02 ) . There was no difference in survival . PSA and objective responses were observed in 32 % and 7 % , respectively , of patients receiving deferred K , and were more common in patients with prior AAWD response . Treatment with K was well tolerated , and result ed in a decline in adrenal and rogen levels , which rose at the time of disease progression . CONCLUSION K has modest activity in AiPCa patients , while AAWD alone has minimal activity . Adrenal and rogen levels fall with treatment with K and then climb at the time of progression , suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of Purpose Advanced prostate cancer ( PC ) is associated with substantial psychosocial morbidity . We sought to determine whether mindfulness-based cognitive therapy ( MBCT ) reduces distress in men with advanced PC . Methods Men with advanced PC ( proven metastatic and /or castration-resistant biochemical progression ) were r and omly assigned to an 8-week , group-based MBCT intervention delivered by telephone ( n = 94 ) or to minimally enhanced usual care ( n = 95 ) . Primary intervention outcomes were psychological distress , cancer-specific distress , and prostate-specific antigen anxiety . Mindfulness skills were assessed as potential mediators of effect . Participants were assessed at baseline and were followed up at 3 , 6 , and 9 months . Main statistical analyses were conducted on the basis of intention to treat . Results Fourteen MBCT groups were conducted in the intervention arm . Facilitator adherence ratings were high ( > 93 % ) . Using r and om-effects mixed-regression models , intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care . Per- protocol analyses also found no differences between arms in outcomes or engagement , with the exception of the mindfulness skill of observing , which increased over time for men in MBCT compared with usual care ( P = .032 ) . Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC . Future intervention research for these men should consider approaches that map more closely to masculinity 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 : Patients who develop castration-resistant prostate cancer ( CRPCa ) typically continue on and rogen deprivation therapy ( ADT ) . Whether these patients need to remain on ADT has not been well studied . We conducted a multicenter r and omized trial to compare an intermittent versus continuous approach to ADT in CRPCa patients .  Overall survival , health-related quality of life ( QOL ) , and cost were the main endpoints . Methods : CRPCa patients were r and omized 2:1 to intermittent or continuous luteinizing hormone-releasing hormone agonists ( LHRHa ) .  Patients were followed with clinical assessment s , laboratory investigations , and QOL question naires ( EORTC QLQ-C30 or PROSQOLI ) every 2 months . If the serum testosterone rose above castrate levels ( 1.75 nmol/L ) , LHRHa were reinitiated . The study was design ed to close if > 50 % of patients needed to restart ADT in the intermittent arm . Results : Thirty-one patients were followed with a median follow-up of 26.8 months—18 in the intermittent arm and 13 in the continuous . Twelve of 18 patients on the intermittent arm were reinitiated on LHRHa at a median time of 17.9 months . There was no difference in overall or cancer-specific survival between the 2 arms . There was no statistically significant difference in QOL between the 2 arms at 0 and 12 months . The total mean costs at 24 months were significantly lower in the intermittent arm ( $ 3135 vs. $ 8253 Canadian dollars , P=0.0167 ) compared with the continuous . The main limitation of this study is the small sample size . Conclusions : We have observed that intermittent ADT in patients with CRPCa , using a testosterone of > 1.75 ngmol/L as a trigger to reinitiate LHRHa , results in a substantial cost savings with no negative impact on oncologic and QOL outcomes Background Prostate cancer ( PCa ) is the most common non-skin cancer among men in developed countries . Several novel treatments have been adopted by healthcare systems to manage PCa . Most of the observational studies and r and omized trials on PCa have concurrently evaluated fewer treatments over short follow-up . Further , preceding decision analytic models on PCa management have not evaluated various contemporary management options . Therefore , a contemporary decision analytic model was necessary to address limitations to the literature by synthesizing the evidence on novel treatments thereby forecasting short and long-term clinical outcomes . Objectives To develop and vali date a Markov Monte Carlo model for the contemporary clinical management of PCa , and to assess the clinical burden of the disease from diagnosis to end-of-life . Methods A Markov Monte Carlo model was developed to simulate the  management  of  PCa in men 65 years and older from diagnosis to end-of-life . Health states modeled were : risk at diagnosis , active surveillance , active treatment , PCa recurrence , PCa recurrence free , metastatic castrate resistant prostate cancer , overall and PCa death . Treatment trajectories were based on state transition probabilities derived from the literature . Validation and sensitivity analyses assessed the accuracy and robustness of model predicted outcomes . Results Validation indicated model predicted rates were comparable to observed rates in the published literature . The simulated distribution of clinical outcomes for the base case was consistent with sensitivity analyses . Predicted rate of clinical outcomes and mortality varied across risk groups . Life expectancy and health adjusted life expectancy predicted for the simulated cohort was 20.9 years ( 95%CI 20.5–21.3 ) and 18.2 years ( 95 % CI 17.9–18.5 ) , respectively . Conclusion Study findings indicated contemporary management strategies improved survival and quality of life in patients with PCa . This model could be used to compare long-term outcomes and life expectancy conferred of PCa management paradigms Purpose Sipuleucel-T , the first FDA -approved autologous cellular immunotherapy for treatment of advanced prostate cancer , is manufactured by activating peripheral blood mononuclear cells , including antigen presenting cells ( APCs ) , with a fusion protein containing prostatic acid phosphatase . Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses , and to relate the immunological responses to overall survival ( OS ) . Methods Sipuleucel-T product characteristics [ APC numbers , APC activation ( CD54 upregulation ) , and total nucleated cell ( TNC ) numbers ] were assessed in three r and omized , controlled phase 3 studies ( N = 737 ) .  Antigen-specific cellular and humoral responses were assessed in a subset of subjects . The relationships between these parameters and OS were assessed . Results APC activation occurred in the first dose preparation [ 6.2-fold , ( 4.65 , 7.70 ) ; median ( 25th , 75th percentile ) ] and increased in the second [ 10.6-fold ( 7.83 , 13.65 ) ] and third [ 10.5-fold ( 7.89 , 13.6 
    Output:
    
The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality -adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations .