***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 
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    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 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 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 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 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 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 
    Output:
    
Two recent , large trials reported improved overall survival with docetaxel-based chemotherapy compared to mitoxantrone-prednisone .
Improved progression-free survival and rates of palliative and objective response were also observed .
Compared with mitoxantrone , docetaxel treatment was associated with more frequent mild toxicities , similar rates of serious toxicities , and better quality of life .
More frequent serious toxicities were observed when docetaxel was combined with estramustine .
Conclusion Docetaxel-based chemotherapy modestly improves survival and provides palliation for men with HRPC and metastases .
Other than and rogen deprivation therapy , this is the only other therapy to have demonstrated improved overall survival in prostate cancer in RCTs .