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 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 Estramustine and etoposide ( VP-16 ) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models . This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy . PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d , were administered orally in divided doses for 21 days . Patients were then taken off therapy for 7 days and the cycle then repeated . Therapy continued until evidence of disease progression . RESULTS Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up . Of 18 patients with measurable soft tissue disease , three demonstrated a complete response ( CR ) and six a partial response ( PR ) for longer than 2 months . Of these 18 patients , pretreatment prostate-specific antigen ( PSA ) levels decreased by at least 75 % in five men ( 28 % ) and by at least 50 % in nine ( 50 % ) . The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria . Of 24 patients with disease limited to bone , six ( 25 % ) demonstrated improvement and nine ( 38 % ) demonstrated stability in their bone scans . Five men ( 21 % ) demonstrated a decrease of at least 75 % in pretreatment PSA levels and 14 ( 58 % ) demonstrated at least a 50 % decrease ; the median survival duration has not been reached in these patients . Pretreatment performance status is an important predictor of survival . CONCLUSION We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer The effect of a medroxyprogesterone acetate ( MPA ) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospect ively r and omized patients with hormone-resistant prostatic cancer . The estimated probability of being free from progression after 1 year was 17 % for the patients treated with estramustine and 29 % for the MPA-epirubicin group . There is a significant difference between the two groups regarding risk of progression ( p = 0.013 ) . However , no difference in survival was recorded ( p > 0.30 ) with about 60 % of the patients dead during the first year in both groups . Progression was highly correlated to sedimentation rate ( p < 0.001 ) and to performance index ( p = 0.002 ) . Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy Single and combination chemotherapy was compared in a clinical trial for men with advanced , metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy . The 149 patients were r and omized to receive estramustine phosphate or cis-platinum alone or in combination .  Of the 149 patients 25 ( 17 per cent ) were excluded from the study but 124 were evaluated for response and survival . Entry variables were distributed similarly among patients in each treatment arm . There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized ( 33 per cent ) on the combination regimen compared to estramustine phosphate ( 18 per cent ) and about a third more than for cis-platinum ( 21 per cent ) . Analysis of survival revealed some advantage for patients on combination therapy .  Major toxicities for all treatments were nausea and vomiting ( 62 to 88 per cent ) and accompanying anorexia ( 72 to 95 per cent ) . Azotemia developed in 45 per cent of the patients receiving combination therapy . In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone . Myelosuppression occurred infrequently 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 Cisobitan , an organosilicon compound with estrogenic and antigonadotropic properties has been evaluated clinical ly in comparison with an estrogen preparation . In a multicenter study a total of 140 patients with well and moderately well differentiated prostatic cancer were r and omly allocated to treatment with Cisobitan or Estradurin/Etivex , 70 to each group . Of 34 patients with poorly differentiated prostatic cancer 18 were given Cisobitan--  and 16 were given  Estracyt-treatment . Among the patients with well and moderately well differentiated prostatic cancer there were , disregarding mortality , no major differences in subjective , objective or laboratory response to the two kinds of treatment . The pattern of side effects was similar , but oedema requiring diuretics occurred more often in the estrogen treated group . There was a significant difference in mortality at 12 months between the groups , two in the Cisobitan group and ten in the estrogen treated group . Cancer was the cause of death in two patients in the estrogen treated group . All other patients succumbed in cardiovascular diseases . At 24 months the difference in mortality rate was less pronounced : Another ten patients had died in the Cisobitan treated group and seven among the estrogen treated patients . Cancer was responsible for the deaths in seven of the Cisobitan patients compared to four of the estrogen treated patients . Within three years one more patient in both groups had died . Of the 34 patients with poorly differentiated cancer , twelve were alive at the 24 months ' follow up , six in the Cisobitan group and six in the Estracyt group OBJECTIVES Results of cytotoxic chemotherapy for hormone-resistant prostate cancer are not impressive . One of the substances which seems to have a therapeutic benefit is 5-fluorouracil ( 5-FU ) . The effect of 5-FU can be modulated by addition of folinic acid ( FA ) . We tested in a prospect i ve , r and omized phase II trial monotherapy with 5-FU versus the combination of 5-FU and high-dose FA . METHODS 25 patients received 600 mg/m2 5-FU , and 24 patients 400 mg/m2 FA plus 600 or 400 mg/m2 5-FU .  They were treated for two cycles for 5 days in a 21-day interval followed by a weekly single-day application until progression occurred . Pain remission , toxicity , time to progression and survival were evaluated . RESULTS Both regimens led to a pain remission in nearly 70 % of the patients . Mucosal side effects like diarrhea and stomatitis occurred more often in the combination arm , whereas leukopenias were more frequent in the monotherapy are . We observed no statistically significant difference between the two treatment arms regarding time to progression and survival . CONCLUSIONS Although both regimens led to a pain remission , side effects are too severe to recommend these protocol s for st and ard treatment of hormone-resistant prostate cancer Abstract In this second nationally r and omized cooperative chemotherapy trial of the National Prostatic Cancer Project 125 patients with histologically confirmed progressing advanced carcinoma of the prostate ( clinical stage D ) who had had prior pelvic irradiation of at least 2,000R received as initial therapy 1 of 2 non-myelosuppressive agents — estramustine phosphate or streptozotocin — for comparison with patients r and omized to receive st and ard treatment . Patients whose disease was progressive after 12 weeks on chemotherapy were crossed over to receive the alternate therapeutic agent . Response to treatment was evaluated in 105 patients on the basis of previously established and defined criteria .All known prognostic factors were comparable among the 3 treatment arms . The objective response rates to therapy were 19 per cent in the st and ard arm ( stable only ) , 30 per cent in the estramustine phosphate arm ( stable and partial regression ) and 32 per cent in the streptozotocin arm ( stable arm ) . Thus far , 4 patients One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride ( Adriamycin ) . Fifty-seven were part of a r and omized study comparing doxorubicin and prednisone to prednisone alone . There were significantly more subjective responders in the doxorubicin group than in the prednisone group ( p less than 0.01 ) . The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone ( p = 0.02 ) . Patients taking do 
    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 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 Estramustine and etoposide ( VP-16 ) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models . This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy . PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d , were administered orally in divided doses for 21 days . Patients were then taken off therapy for 7 days and the cycle then repeated . Therapy continued until evidence of disease progression . RESULTS Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up . Of 18 patients with measurable soft tissue disease , three demonstrated a complete response ( CR ) and six a partial response ( PR ) for longer than 2 months . Of these 18 patients , pretreatment prostate-specific antigen ( PSA ) levels decreased by at least 75 % in five men ( 28 % ) and by at least 50 % in nine ( 50 % ) . The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria . Of 24 patients with disease limited to bone , six ( 25 % ) demonstrated improvement and nine ( 38 % ) demonstrated stability in their bone scans . Five men ( 21 % ) demonstrated a decrease of at least 75 % in pretreatment PSA levels and 14 ( 58 % ) demonstrated at least a 50 % decrease ; the median survival duration has not been reached in these patients . Pretreatment performance status is an important predictor of survival . CONCLUSION We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer The effect of a medroxyprogesterone acetate ( MPA ) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospect ively r and omized patients with hormone-resistant prostatic cancer . The estimated probability of being free from progression after 1 year was 17 % for the patients treated with estramustine and 29 % for the MPA-epirubicin group . There is a significant difference between the two groups regarding risk of progression ( p = 0.013 ) . However , no difference in survival was recorded ( p > 0.30 ) with about 60 % of the patients dead during the first year in both groups . Progression was highly correlated to sedimentation rate ( p < 0.001 ) and to performance index ( p = 0.002 ) . Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy Single and combination chemotherapy was compared in a clinical trial for men with advanced , metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy . The 149 patients were r and omized to receive estramustine phosphate or cis-platinum alone or in combination .  Of the 149 patients 25 ( 17 per cent ) were excluded from the study but 124 were evaluated for response and survival . Entry variables were distributed similarly among patients in each treatment arm . There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized ( 33 per cent ) on the combination regimen compared to estramustine phosphate ( 18 per cent ) and about a third more than for cis-platinum ( 21 per cent ) . Analysis of survival revealed some advantage for patients on combination therapy .  Major toxicities for all treatments were nausea and vomiting ( 62 to 88 per cent ) and accompanying anorexia ( 72 to 95 per cent ) . Azotemia developed in 45 per cent of the patients receiving combination therapy . In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone . Myelosuppression occurred infrequently 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 Cisobitan , an organosilicon compound with estrogenic and antigonadotropic properties has been evaluated clinical ly in comparison with an estrogen preparation . In a multicenter study a total of 140 patients with well and moderately well differentiated prostatic cancer were r and omly allocated to treatment with Cisobitan or Estradurin/Etivex , 70 to each group . Of 34 patients with poorly differentiated prostatic cancer 18 were given Cisobitan--  and 16 were given  Estracyt-treatment . Among the patients with well and moderately well differentiated prostatic cancer there were , disregarding mortality , no major differences in subjective , objective or laboratory response to the two kinds of treatment . The pattern of side effects was similar , but oedema requiring diuretics occurred more often in the estrogen treated group . There was a significant difference in mortality at 12 months between the groups , two in the Cisobitan group and ten in the estrogen treated group . Cancer was the cause of death in two patients in the estrogen treated group . All other patients succumbed in cardiovascular diseases . At 24 months the difference in mortality rate was less pronounced : Another ten patients had died in the Cisobitan treated group and seven among the estrogen treated patients . Cancer was responsible for the deaths in seven of the Cisobitan patients compared to four of the estrogen treated patients . Within three years one more patient in both groups had died . Of the 34 patients with poorly differentiated cancer , twelve were alive at the 24 months ' follow up , six in the Cisobitan group and six in the Estracyt group OBJECTIVES Results of cytotoxic chemotherapy for hormone-resistant prostate cancer are not impressive . One of the substances which seems to have a therapeutic benefit is 5-fluorouracil ( 5-FU ) . The effect of 5-FU can be modulated by addition of folinic acid ( FA ) . We tested in a prospect i ve , r and omized phase II trial monotherapy with 5-FU versus the combination of 5-FU and high-dose FA . METHODS 25 patients received 600 mg/m2 5-FU , and 24 patients 400 mg/m2 FA plus 600 or 400 mg/m2 5-FU .  They were treated for two cycles for 5 days in a 21-day interval followed by a weekly single-day application until progression occurred . Pain remission , toxicity , time to progression and survival were evaluated . RESULTS Both regimens led to a pain remission in nearly 70 % of the patients . Mucosal side effects like diarrhea and stomatitis occurred more often in the combination arm , whereas leukopenias were more frequent in the monotherapy are . We observed no statistically significant difference between the two treatment arms regarding time to progression and survival . CONCLUSIONS Although both regimens led to a pain remission , side effects are too severe to recommend these protocol s for st and ard treatment of hormone-resistant prostate cancer Abstract In this second nationally r and omized cooperative chemotherapy trial of the National Prostatic Cancer Project 125 patients with histologically confirmed progressing advanced carcinoma of the prostate ( clinical stage D ) who had had prior pelvic irradiation of at least 2,000R received as initial therapy 1 of 2 non-myelosuppressive agents — estramustine phosphate or streptozotocin — for comparison with patients r and omized to receive st and ard treatment . Patients whose disease was progressive after 12 weeks on chemotherapy were crossed over to receive the alternate therapeutic agent . Response to treatment was evaluated in 105 patients on the basis of previously established and defined criteria .All known prognostic factors were comparable among the 3 treatment arms . The objective response rates to therapy were 19 per cent in the st and ard arm ( stable only ) , 30 per cent in the estramustine phosphate arm ( stable and partial regression ) and 32 per cent in the streptozotocin arm ( stable arm ) . Thus far , 4 patients One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride ( Adriamycin ) . Fifty-seven were part of a r and omized study comparing doxorubicin and prednisone to prednisone alone . There were significantly more subjective responders in the doxorubicin group than in the prednisone group ( p less than 0.01 ) . The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone ( p = 0.02 ) . Patients taking do 
    Output:
    