human
***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 PURPOSE To assess whether the risk of death is associated with the time to testosterone recovery ( TTR ) after radiotherapy ( RT ) and hormonal therapy ( HT ) for prostate cancer ( PCa ) . PATIENTS AND METHODS Between 1995 and 2001 , 206 men with localized , unfavorable-risk PCa were r and omized to receive RT or RT plus 6 months of HT . A multivariate postr and omization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors , age , Adult Comorbidity Evaluation-27 score , and the use of HT for recurrence . RESULTS Of the 102 men r and omized to receive RT and HT  , 57 ( 56 % ) had a TTR of > 2 years , and none of these men had died of PCa after a median follow-up of 7.6 years . As the TTR increased , the risk of death decreased significantly ( adjusted hazard ratio , 0.60 ; 95 % confidence interval , 0.43 - 0.84 ; p = .003 ) . A significant interaction was noted between the TTR and the comorbidity score ( p = .002 ) . The survival estimates were similar ( p = 0.17 ) across the TTR values in men with moderate to severe comorbidity ; however , these estimates increased significantly ( p < .001 ) with decreasing PCa-specific mortality ( p = .006 ) as the TTR increased in men with no or minimal comorbidity . CONCLUSION The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity We conducted a r and omized clinical trial in men with stage D2 prostate cancer to test whether and rogen priming potentiates the efficacy of cytotoxic chemotherapy .  Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal and rogen secretion and were administered cyclic intravenous ( IV ) chemotherapy . The patients were r and omized to receive either and rogen priming or no additional treatment for three days before and on the day of chemotherapy . Median duration of follow-up was 43 months . Response rate ( remission plus disease stabilization ) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients ( 79 % v 73 % , respectively ) or when it was extended to all patients ( 46 % v 61 % ) . Median duration of response was similar for the stimulation and control arm ( 9 and 10 months , respectively ) . Median survival was 10 months in the stimulation and 15 months in the control group ( P = .0047 ) . The and rogen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with and rogen administration . Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit , long duration of response to the initial castration , and normalization of an elevated serum acid phosphatase on treatment . We conclude that in this group of patients with advanced disease , and rogen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome . Furthermore , our data emphasize the heterogeneity of biologic behavior of prostate cancer To evaluate the efficacy and safety of degarelix , a new gonadotrophin‐releasing hormone ( GnRH ) antagonist ( blocker ) , vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer PURPOSE Few patients with locally recurrent prostate cancer after external beam ( EB ) or interstitial ( I ) radiotherapy ( RT )  are considered c and i date s for salvage radical prostatectomy ( RP ) due to high reported rates of major complications and urinary incontinence . We report the morbidity associated with salvage RP in 100 consecutive patients . MATERIAL S AND METHODS From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases , and IRT in 42 ( 28 retropubic ) and ( 14 transperineal ) . Clinical information was obtained from a prospect i ve data base . RESULTS Since 1993 , the major complication rate has decreased significantly ( 13 % vs 33 % , p = 0.02 ) , including the rectal injury rate ( 2 % vs 15 % , p = 0.01 ) . Compared with retropubic IRT and /or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less ( OR 0.2 , p = 0.006 ) . At 5 years an estimated 39 % of patients were dry and 68 % required 1 pad daily or less . A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement . The anastomotic stricture rate was 30 % . The 5-year potency rate was 28 % following unilateral or bilateral nerve sparing RP and 45 % in previously potent patients . CONCLUSIONS Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of st and ard RP . Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after st and ard RP . However , most patients recover reasonable urinary continence and a substantial number of select patients recover potency . The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit PURPOSE Prostate-specific antigen ( PSA ) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells . For patients with metastatic disease , changes in PSA will often ante date changes in bone scan . Furthermore , many but not all investigators have observed an association between a decline in PSA levels of 50 % or greater and survival . Since the majority of phase II clinical trials for patients with and rogen-independent prostate cancer ( AIPC ) have used PSA as a marker , we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting . We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters . RESULT We defined four patient groups : ( 1 ) progressive measurable disease , ( 2 ) progressive bone metastasis , ( 3 ) stable metastases and a rising PSA , and ( 4 ) rising PSA and no other evidence of metastatic disease .  The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials . We propose that investigators report at a minimum a PSA decline of at least 50 % and this must be confirmed by a second PSA value 4 or more weeks later . Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period . Some investigators may want to report additional measures of PSA changes ( ie , 75 % decline , 90 % decline ) . Response duration and the time to PSA progression may also be important clinical end point . CONCLUSION Through this consensus conference , we believe we have developed practical guidelines for using PSA as a measurement of outcome . Furthermore , the use of common st and ards is important as we determine which agents should progress to r and omized trials which will use survival as an end point BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( 
    Output:
    
agent
LHRH antagonists decrease testosterone without any testosterone surge , and they may be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
LHRH antagonists decrease testosterone without any testosterone surge , and they might be associated with an oncologic benefit compared with LHRH analogues .
Complete and rogen blockade has a small survival benefit of about 5 % .
Intermittent and rogen deprivation results in noninferior oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT .
***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 PURPOSE To assess whether the risk of death is associated with the time to testosterone recovery ( TTR ) after radiotherapy ( RT ) and hormonal therapy ( HT ) for prostate cancer ( PCa ) . PATIENTS AND METHODS Between 1995 and 2001 , 206 men with localized , unfavorable-risk PCa were r and omized to receive RT or RT plus 6 months of HT . A multivariate postr and omization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors , age , Adult Comorbidity Evaluation-27 score , and the use of HT for recurrence . RESULTS Of the 102 men r and omized to receive RT and HT  , 57 ( 56 % ) had a TTR of > 2 years , and none of these men had died of PCa after a median follow-up of 7.6 years . As the TTR increased , the risk of death decreased significantly ( adjusted hazard ratio , 0.60 ; 95 % confidence interval , 0.43 - 0.84 ; p = .003 ) . A significant interaction was noted between the TTR and the comorbidity score ( p = .002 ) . The survival estimates were similar ( p = 0.17 ) across the TTR values in men with moderate to severe comorbidity ; however , these estimates increased significantly ( p < .001 ) with decreasing PCa-specific mortality ( p = .006 ) as the TTR increased in men with no or minimal comorbidity . CONCLUSION The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity We conducted a r and omized clinical trial in men with stage D2 prostate cancer to test whether and rogen priming potentiates the efficacy of cytotoxic chemotherapy .  Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal and rogen secretion and were administered cyclic intravenous ( IV ) chemotherapy . The patients were r and omized to receive either and rogen priming or no additional treatment for three days before and on the day of chemotherapy . Median duration of follow-up was 43 months . Response rate ( remission plus disease stabilization ) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients ( 79 % v 73 % , respectively ) or when it was extended to all patients ( 46 % v 61 % ) . Median duration of response was similar for the stimulation and control arm ( 9 and 10 months , respectively ) . Median survival was 10 months in the stimulation and 15 months in the control group ( P = .0047 ) . The and rogen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with and rogen administration . Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit , long duration of response to the initial castration , and normalization of an elevated serum acid phosphatase on treatment . We conclude that in this group of patients with advanced disease , and rogen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome . Furthermore , our data emphasize the heterogeneity of biologic behavior of prostate cancer To evaluate the efficacy and safety of degarelix , a new gonadotrophin‐releasing hormone ( GnRH ) antagonist ( blocker ) , vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer PURPOSE Few patients with locally recurrent prostate cancer after external beam ( EB ) or interstitial ( I ) radiotherapy ( RT )  are considered c and i date s for salvage radical prostatectomy ( RP ) due to high reported rates of major complications and urinary incontinence . We report the morbidity associated with salvage RP in 100 consecutive patients . MATERIAL S AND METHODS From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases , and IRT in 42 ( 28 retropubic ) and ( 14 transperineal ) . Clinical information was obtained from a prospect i ve data base . RESULTS Since 1993 , the major complication rate has decreased significantly ( 13 % vs 33 % , p = 0.02 ) , including the rectal injury rate ( 2 % vs 15 % , p = 0.01 ) . Compared with retropubic IRT and /or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less ( OR 0.2 , p = 0.006 ) . At 5 years an estimated 39 % of patients were dry and 68 % required 1 pad daily or less . A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement . The anastomotic stricture rate was 30 % . The 5-year potency rate was 28 % following unilateral or bilateral nerve sparing RP and 45 % in previously potent patients . CONCLUSIONS Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of st and ard RP . Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after st and ard RP . However , most patients recover reasonable urinary continence and a substantial number of select patients recover potency . The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit PURPOSE Prostate-specific antigen ( PSA ) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells . For patients with metastatic disease , changes in PSA will often ante date changes in bone scan . Furthermore , many but not all investigators have observed an association between a decline in PSA levels of 50 % or greater and survival . Since the majority of phase II clinical trials for patients with and rogen-independent prostate cancer ( AIPC ) have used PSA as a marker , we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting . We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters . RESULT We defined four patient groups : ( 1 ) progressive measurable disease , ( 2 ) progressive bone metastasis , ( 3 ) stable metastases and a rising PSA , and ( 4 ) rising PSA and no other evidence of metastatic disease .  The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials . We propose that investigators report at a minimum a PSA decline of at least 50 % and this must be confirmed by a second PSA value 4 or more weeks later . Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period . Some investigators may want to report additional measures of PSA changes ( ie , 75 % decline , 90 % decline ) . Response duration and the time to PSA progression may also be important clinical end point . CONCLUSION Through this consensus conference , we believe we have developed practical guidelines for using PSA as a measurement of outcome . Furthermore , the use of common st and ards is important as we determine which agents should progress to r and omized trials which will use survival as an end point BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( 
    Output:
    