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: Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death . Adjuvant and rogen-deprivation therapy ( ADT ) may reduce this risk . We hypothesized that the addition of mitoxantrone and prednisone ( MP ) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone . Methods Eligible patients had cT1 - 3N0 prostate cancer with one or more high-risk factors after radical prostatectomy ( Gleason score [ GS ] ≥ 8 ; pT3b , pT4 , or pN+ disease ; GS 7 and positive margins ; or preoperative prostate-specific antigen [ PSA ] > 15 ng/mL , biopsy GS score > 7 , or PSA > 10 ng/mL plus biopsy GS > 6 . Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage , GS , and adjuvant radiation plan and r and omly assigned to ADT ( bicalutamide and goserelin for 2 years ) or ADT plus six cycles of MP . The primary end point was overall survival ( OS ) . Median OS was projected to be 10 years in the ADT arm , requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92 % power and one-sided α = .05 . Results Nine hundred sixty-one eligible intent-to-treat patients were r and omly assigned to ADT or ADT + MP from October 1999 to January 2007 , when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP . Median follow-up was 11.2 years . The 10-year OS estimates were 87 % with ADT ( expected 50 % ) and 86 % with ADT + MP ( hazard ratio , 1.06 ; 95 % CI , 0.79 to 1.43 ) . The 10-year estimate for disease-free survival was 72 % for both arms . Prostate cancer was the cause of death in 18 % of patients in the ADT arm and 22 % in the ADT + MP arm . More patients in the MP arm died of other cancers ( 36 % v 18 % in ADT alone arm ) . Conclusion MP did not improve OS and increased deaths from other malignancies . The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates , although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm PURPOSE Long-term and rogen suppression plus radiotherapy ( AS+RT ) is st and ard treatment of high-risk prostate cancer . A r and omized trial , Radiation Therapy Oncology Group trial 9902 , was undertaken to determine whether adjuvant chemotherapy with paclitaxel , estramustine , and etoposide ( TEE ) plus AS+RT would improve disease outcomes with acceptable toxicity . METHODS AND MATERIAL S High-risk ( prostate-specific antigen 20 - 100 ng/mL and Gleason score > or=7 ; or Stage T2 or greater , Gleason score 8 , prostate-specific antigen level < 100 ng/mL ) nonmetastatic prostate cancer patients were r and omized to AS+RT ( Arm 1 ) vs. AS+RT plus four cycles of TEE ( Arm 2 ) . TEE was delivered 4 weeks after RT . AS continued for 2 years for both treatment arms . RT began after 8 weeks of AS began . RESULTS The Radiation Therapy Oncology Group 9902 trial opened January 11 , 2000 . Excess thromboembolic toxicity was noted , leading to study closure October 4 , 2004 . A total of 397 patients were accrued , and the data for 381 were analyzable . An acute and long-term toxicity analysis was performed . The worst overall toxicities during treatment were increased for Arm 2 . Of the 192 patients , 136 ( 71 % ) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 ( 37 % ) of 189 patients on Arm 1 . Statistically significant increases in hematologic toxicity ( p < 0.0001 ) and gastrointestinal toxicity ( p = 0.017 ) but not genitourinary toxicity ( p = 0.07 ) were noted during treatment . Two Grade 5 complications related to neutropenic infection occurred in Arm 2 . Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2 . At 2 and 3 years after therapy completion , excess long-term toxicity was not observed in Arm 2 . CONCLUSION TEE was associated with significantly increased toxicity during treatment . The toxicity profiles did not differ at 2 and 3 years after therapy . Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer Purpose : The TAX-327 study r and omized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel , weekly docetaxel , or mitoxantrone , each with prednisone . Experimental Design : We used the TAX-327 data base to address ( a ) the relationship between quality of life ( QoL ) and pain ; ( b ) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL ; ( c ) the relationships between prostate-specific antigen ( PSA ) response , pain response , and QoL response ; ( d ) the times at which these responses are first observed ; and ( e ) whether PSA , pain , and /or QoL response predict for overall survival . Results : At baseline , 374 of 815 men assessed for QoL had major pain ; of these , 92 % had substantial impairment of QoL compared with 75 % without major pain ( P < 0.001 ) . Men with minimal symptoms had prolonged survival ( median , 25.6 months ) compared with symptomatic patients ( median , 17.1 months ; P = 0.009 ) ; they were more likely to have initial deterioration of QoL if treated with weekly docetaxel .  PSA response and pain response , but not QoL response , were independently associated with survival in l and mark analysis . Median times to PSA and pain response were 44 and 27 days , respectively ; some men had initial increase in serum PSA before subsequent decline . Conclusions : Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer . Those with minimal symptoms have prolonged survival . Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies . Early increases in serum PSA ( up to 12 weeks ) should be ignored when determining response or progression CONTEXT Interstitial radiation ( implant ) therapy is used to treat clinical ly localized adenocarcinoma of the prostate , but how it compares with other treatments is not known . OBJECTIVE To estimate control of prostate-specific antigen ( PSA ) after radical prostatectomy ( RP ) , external beam radiation ( RT ) , or implant with or without neoadjuvant and rogen deprivation therapy in patients with clinical ly localized prostate cancer . DESIGN Retrospective cohort study of outcome data compared using Cox regression multivariable analyses . SETTING AND PATIENTS A total of 1872 men treated between January 1989 and October 1997 with an RP ( n = 888 ) or implant with or without neoadjuvant and rogen deprivation therapy ( n = 218 ) at the Hospital of the University of Pennsylvania , Philadelphia , or RT ( n = 766 ) at the Joint Center for Radiation Therapy , Boston , Mass , were enrolled . MAIN OUTCOME MEASURE Actuarial freedom from PSA failure ( defined as PSA outcome ) . RESULTS The relative risk ( RR ) of PSA failure in low-risk patients ( stage T1c , T2a and PSA level < or = 10 ng/mL and Gleason score < or = 6 ) treated using RT , implant plus and rogen deprivation therapy , or implant therapy was 1.1 ( 95 % confidence interval [ CI ] , 0.5 - 2.7 ) , 0.5 ( 95 % CI , 0.1 - 1.9 ) , and 1.1 ( 95 % CI , 0.3 - 3.6 ) , respectively , compared with those patients treated with RP . The RRs of PSA failure in the intermediate-risk patients ( stage T2b or Gleason score of 7 or PSA level > 10 and < or = 20 ng/mL ) and high-risk patients ( stage T2c or PSA level > 20 ng/mL or Gleason score > or = 8) treated with implant compared with RP were 3.1 ( 95 % CI , 1.5 - 6.1 ) and 3.0 ( 95 % CI , 1.8 - 5.0 ) , respectively . The addition of and rogen deprivation to implant therapy did not improve PSA outcome in high-risk patients but result ed in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients . These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10 . CONCLUSIONS Low-risk patients had estimates of 5-year PSA outcome after treatment with RP , RT , or implant with or without neoadjuvant and rogen deprivation that were not statistically different , whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant . Prospect i ve r and omized trials are needed to verify these findings 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 N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade  
    Output:
    
agent
***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 Patients with high-risk prostate cancer after radical prostatectomy are at risk for death . Adjuvant and rogen-deprivation therapy ( ADT ) may reduce this risk . We hypothesized that the addition of mitoxantrone and prednisone ( MP ) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone . Methods Eligible patients had cT1 - 3N0 prostate cancer with one or more high-risk factors after radical prostatectomy ( Gleason score [ GS ] ≥ 8 ; pT3b , pT4 , or pN+ disease ; GS 7 and positive margins ; or preoperative prostate-specific antigen [ PSA ] > 15 ng/mL , biopsy GS score > 7 , or PSA > 10 ng/mL plus biopsy GS > 6 . Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage , GS , and adjuvant radiation plan and r and omly assigned to ADT ( bicalutamide and goserelin for 2 years ) or ADT plus six cycles of MP . The primary end point was overall survival ( OS ) . Median OS was projected to be 10 years in the ADT arm , requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92 % power and one-sided α = .05 . Results Nine hundred sixty-one eligible intent-to-treat patients were r and omly assigned to ADT or ADT + MP from October 1999 to January 2007 , when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP . Median follow-up was 11.2 years . The 10-year OS estimates were 87 % with ADT ( expected 50 % ) and 86 % with ADT + MP ( hazard ratio , 1.06 ; 95 % CI , 0.79 to 1.43 ) . The 10-year estimate for disease-free survival was 72 % for both arms . Prostate cancer was the cause of death in 18 % of patients in the ADT arm and 22 % in the ADT + MP arm . More patients in the MP arm died of other cancers ( 36 % v 18 % in ADT alone arm ) . Conclusion MP did not improve OS and increased deaths from other malignancies . The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates , although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm PURPOSE Long-term and rogen suppression plus radiotherapy ( AS+RT ) is st and ard treatment of high-risk prostate cancer . A r and omized trial , Radiation Therapy Oncology Group trial 9902 , was undertaken to determine whether adjuvant chemotherapy with paclitaxel , estramustine , and etoposide ( TEE ) plus AS+RT would improve disease outcomes with acceptable toxicity . METHODS AND MATERIAL S High-risk ( prostate-specific antigen 20 - 100 ng/mL and Gleason score > or=7 ; or Stage T2 or greater , Gleason score 8 , prostate-specific antigen level < 100 ng/mL ) nonmetastatic prostate cancer patients were r and omized to AS+RT ( Arm 1 ) vs. AS+RT plus four cycles of TEE ( Arm 2 ) . TEE was delivered 4 weeks after RT . AS continued for 2 years for both treatment arms . RT began after 8 weeks of AS began . RESULTS The Radiation Therapy Oncology Group 9902 trial opened January 11 , 2000 . Excess thromboembolic toxicity was noted , leading to study closure October 4 , 2004 . A total of 397 patients were accrued , and the data for 381 were analyzable . An acute and long-term toxicity analysis was performed . The worst overall toxicities during treatment were increased for Arm 2 . Of the 192 patients , 136 ( 71 % ) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 ( 37 % ) of 189 patients on Arm 1 . Statistically significant increases in hematologic toxicity ( p < 0.0001 ) and gastrointestinal toxicity ( p = 0.017 ) but not genitourinary toxicity ( p = 0.07 ) were noted during treatment . Two Grade 5 complications related to neutropenic infection occurred in Arm 2 . Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2 . At 2 and 3 years after therapy completion , excess long-term toxicity was not observed in Arm 2 . CONCLUSION TEE was associated with significantly increased toxicity during treatment . The toxicity profiles did not differ at 2 and 3 years after therapy . Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer Purpose : The TAX-327 study r and omized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel , weekly docetaxel , or mitoxantrone , each with prednisone . Experimental Design : We used the TAX-327 data base to address ( a ) the relationship between quality of life ( QoL ) and pain ; ( b ) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL ; ( c ) the relationships between prostate-specific antigen ( PSA ) response , pain response , and QoL response ; ( d ) the times at which these responses are first observed ; and ( e ) whether PSA , pain , and /or QoL response predict for overall survival . Results : At baseline , 374 of 815 men assessed for QoL had major pain ; of these , 92 % had substantial impairment of QoL compared with 75 % without major pain ( P < 0.001 ) . Men with minimal symptoms had prolonged survival ( median , 25.6 months ) compared with symptomatic patients ( median , 17.1 months ; P = 0.009 ) ; they were more likely to have initial deterioration of QoL if treated with weekly docetaxel .  PSA response and pain response , but not QoL response , were independently associated with survival in l and mark analysis . Median times to PSA and pain response were 44 and 27 days , respectively ; some men had initial increase in serum PSA before subsequent decline . Conclusions : Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer . Those with minimal symptoms have prolonged survival . Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies . Early increases in serum PSA ( up to 12 weeks ) should be ignored when determining response or progression CONTEXT Interstitial radiation ( implant ) therapy is used to treat clinical ly localized adenocarcinoma of the prostate , but how it compares with other treatments is not known . OBJECTIVE To estimate control of prostate-specific antigen ( PSA ) after radical prostatectomy ( RP ) , external beam radiation ( RT ) , or implant with or without neoadjuvant and rogen deprivation therapy in patients with clinical ly localized prostate cancer . DESIGN Retrospective cohort study of outcome data compared using Cox regression multivariable analyses . SETTING AND PATIENTS A total of 1872 men treated between January 1989 and October 1997 with an RP ( n = 888 ) or implant with or without neoadjuvant and rogen deprivation therapy ( n = 218 ) at the Hospital of the University of Pennsylvania , Philadelphia , or RT ( n = 766 ) at the Joint Center for Radiation Therapy , Boston , Mass , were enrolled . MAIN OUTCOME MEASURE Actuarial freedom from PSA failure ( defined as PSA outcome ) . RESULTS The relative risk ( RR ) of PSA failure in low-risk patients ( stage T1c , T2a and PSA level < or = 10 ng/mL and Gleason score < or = 6 ) treated using RT , implant plus and rogen deprivation therapy , or implant therapy was 1.1 ( 95 % confidence interval [ CI ] , 0.5 - 2.7 ) , 0.5 ( 95 % CI , 0.1 - 1.9 ) , and 1.1 ( 95 % CI , 0.3 - 3.6 ) , respectively , compared with those patients treated with RP . The RRs of PSA failure in the intermediate-risk patients ( stage T2b or Gleason score of 7 or PSA level > 10 and < or = 20 ng/mL ) and high-risk patients ( stage T2c or PSA level > 20 ng/mL or Gleason score > or = 8) treated with implant compared with RP were 3.1 ( 95 % CI , 1.5 - 6.1 ) and 3.0 ( 95 % CI , 1.8 - 5.0 ) , respectively . The addition of and rogen deprivation to implant therapy did not improve PSA outcome in high-risk patients but result ed in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients . These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10 . CONCLUSIONS Low-risk patients had estimates of 5-year PSA outcome after treatment with RP , RT , or implant with or without neoadjuvant and rogen deprivation that were not statistically different , whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant . Prospect i ve r and omized trials are needed to verify these findings 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 N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade  
    Output:
    