***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: This multicenter . r and omized study compared the LHRH agonist buserelin with diethylstilbestrol (DES)/or-chiectomy in the treatment of patients with stage D2 prostatic carcinoma . Subjects were r and omized to treatment with buserelin or DES/orchiectomy  in a 2:1 ratio . Data from 160 subjects were available for analysis : 105 buserelin subjects ( 89 s.c . and 16 i.n . ) , 41 DES-treated subjects , and 14 orchiectomized subjects . Either subcutaneous ( 200 ( μ , g q.d . ) or intranasal ( 400 μg t.i.d . ) maintenance doses of buserelin  suppressed serum testosterone values to below castrate levels ( < 100 ng/dl ) by week 3 and maintained suppression for over 24 months . Times to treatment failure for specific reasons were analyzed and compared between treatment groups . There was a significant difference between treatment groups in favor of buserelin in the time to treatment failure due to an adverse event ( p ≤ 0.05 ) . There were no statistically significant differences between the treatment groups in the progression-free survival , best response , and life survival analyses . In addition , buserelin treatment improved quality of life parameters such as pain , performance status , and genitourinary symptoms . With the exception of symptoms of and rogen deficiency , few side effects were reported in the buserelin subjects and most were of a minor nature . The incidence of severe side effects was significantly higher among the DES/orchiectomy subjects To explore the value of anti and rogen therapy for advanced prostate cancer , two clinical trials of similar design were recently conducted in six countries throughout Europe . A total of 550 patients with previously untreated metastatic prostate cancer were r and omized either to treatment with an anti and rogen or castration .  While time to treatment failure , objective tumour response and survival were expected to be similar between study treatments , their effects on health-related quality of life ( HRQOL ) were expected to differ and were therefore a focus of concern in this trial . To assess these effects , we developed a brief self-administered patient question naire covering 10 domains of HRQOL ( general health perceptions , pain , emotional well-being , vitality , social functioning , physical capacity , sexual interest , sexual functioning , activity limitation and bed disability ) , which we translated from English into several other language s. In this paper , we describe the development , content and translation of this survey instrument and report on its reliability and validity in six countries based on data collected for the first 487 patients to complete question naires at study entry OBJECTIVES To compare the efficacy and safety of goserelin and orchiectomy in patients with stage D2 prostate cancer . METHODS A r and omized , open , multicenter study was conducted in 283 patients . Patients were allocated to goserelin , 3.6 mg every 28 days or to orchiectomy . Study end points were endocrine response , objective response , time to treatment failure , survival , and tolerability . Objective response was based on modified criteria of the National Prostate Cancer Project . RESULTS Serum testosterone decreased from baseline to castrate levels by week 4 in each group and remained below castrate levels thereafter . Acid phosphatase and alkaline phosphatase concentrations also decreased in each group . The goserelin and orchiectomy groups had similar results for objective response ( 82 % versus 77 % ) and had similar medial times to treatment failure ( 52 versus 53 weeks ) and survival ( 119 versus 136 weeks ) . No significant interactions between treatments and prognostic factors were observed . Adjusting for baseline testosterone concentration had no effect on survival outcome . Race had no influence on outcome or efficacy end points . Common adverse events in both groups were pain , hot flushes , and lower urinary tract symptoms . CONCLUSIONS Goserelin is well tolerated and as effective as orchiectomy in patients with Stage D2 prostate cancer We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects , efficacy , and safety of 3.6 mg of goserelin acetate ( Zoladex ) and orchiectomy in patients with Stage D2 prostate cancer . Eighty-one patients were r and omly allocated to receive Zoladex and 83 to orchiectomy .  The median follow-up time for all patients was two hundred ten days . Median serum levels of testosterone were reduced to castrate levels ( less than 50 ng/dL ) within four weeks in both groups and remained suppressed for up to sixty weeks . An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups , respectively . There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression . The most commonly reported adverse events in both treatment groups were hot flashes , cancer-related pain , unspecified pain , and urinary symptoms . These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced  prostate cancer OBJECTIVES Single-agent therapy with bicalutamide , a nonsteroidal anti and rogen , was compared with castration , either surgical or medical , in patients with untreated Stage D2 prostate cancer . METHODS In an open , r and omized , multicenter trial , patients were r and omized to treatment with 50 mg bicalutamide ( n = 243 ) once daily or to castration ( n = 243 ) , either orchiectomy or depot injection of goserelin acetate every 28 days . Primary efficacy endpoints were times to treatment failure and objective disease progression and survival . Assessment s included review of measurable metastases , prostate dimensions , Eastern Cooperative Oncology Group performance status , pain , analgesic requirements , and quality of life responses . RESULTS The median duration of therapy was 39 weeks for bicalutamide-treated patients and 42 weeks for castrated patients ; treatment failure occurred in 53 % and 42 % and disease progression in 43 % and 33 % , respectively . Treatment effects favored castration for both endpoints ( P < or = 0.002 ) , with hazard ratios ( bicalutamide : castration ) of 1.54 ( 95 % confidence interval [ CI ] , 1.18 to 2.00 ) for time to treatment failure and 1.6 ( 95 % CI , 1.19 to 2.15 ) for time to disease progression . From the 1-year survival analysis , the hazard ratio for probability of death was 1.29 ( 95 % CI , 0.96 to 1.72 ) . Thus far , with a median follow-up of 86 weeks , median survival has not been reached in either group . Changes from baseline in several quality of life variables were significantly different ( P < or = 0.01 ) between treatment groups periodically from months 1 to 6 , and all favored bicalutamide . Overall , the anti and rogen was well tolerated compared with castration ; with bicalutamide , hot flushes occurred less often and breast tenderness and gynecomastia more often . CONCLUSIONS Although a dosage of 50 mg of bicalutamide once daily was not as effective as castration , the favorable quality of life outcomes and the low incidence of nonhormonal adverse events provide reasons to evaluate bicalutamide , as a single therapeutic agent , at higher doses PURPOSE Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone . Therapy with diethylstilbestrol ( DES ) , leuprolide , or bilateral orchiectomy has been reported to be equivalent . DES is the cheapest preparation , but has the potential for serious cardiovascular or thromboembolic complications .  Flutamide is a novel anti and rogen with fewer side effects . PATIENTS AND METHODS The Eastern Cooperative Oncology Group ( ECOG ) conducted a double-blind , r and omized study to compare the efficacy of flutamide ( 250 mg three times daily ) to DES ( 1 mg three times daily ) as the primary hormonal therapy for patients with stage D2 prostate cancer . Patients were stratified by performance status , disease sites , and history of cardiovascular disease at r and omization . RESULTS Forty-eight patients received DES and 44 flutamide . Patient characteristics were evenly distributed between the two treatments . The overall response rate was similar ( DES , 62 % ; flutamide , 50 % ) . Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3 % of patients on DES and in 17.6 % on flutamide ( P = .051 ) . Other toxicities were similar between the two treatment arms . However , DES produced significantly longer time to treatment failure ( 26.4 v 9.7 months , P = .016 ) and longer survival than flutamide ( 43.2 v 28.5 months , P = .040 ) . CONCLUSION As the primary hormonal therapy for stage D2 prostate cancer , DES caused more serious cardiovascular or thromboembolic complications than flutamide . Despite this , flutamide was not as active an initial agent as DES . However , the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined , and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies OBJECTIVES Bicalutamide is a new , potent anti and rogen with potential efficacy in the treatment of men with advanced prostate cancer . Although no pure anti and rogen has been well studied versus castration , potentially fewer adverse effects could occur , making such an agent a potentially useful alternative therapy . To date , three r and omized controlled trials have been performed comparing these two treatments . In preliminary studies , a dose of 50 mg bicalutamide per day was selected for these trials . In two of the studies ( 0302 , 0303 ) , this drug was compared to either medical or surgical castration , the latter choice being made by the patient . In the third study ( 0301 ) , bicalutamide was compared to bilateral orchiectomy . METHODS Using an intention-to-treat format , the outcomes assessed were time-to-treatment failure , time-to- objective disease progression , subjective response , and survival time in men with previously untreated metastatic disease . The incidence of breast tenderness , gynecomastia , and hot flushes was also determined in both treatment arms . A quality -of-life question naire was administered on multiple occasions after initiation of therapy . RESULTS Based on an analysis of > 1000 patients , the objective and subjective results favored castration over bicalutamide ( 50 mg/day ) . The hazard ratios for time-to-treatment failure ( 1.59 ) , time-to-disease progression ( 1.62 ) , and median survival ( 1.44 ) were all significantly greater in the castration group ( P > 0.001 ) . Another difference noted at 3 months was a significantly lower median fall in prostate-specific antigen values in the bicalutamide group ( 86 - 88 % versus 96 - 97 % ) . Symptomatic patients receiving bicalutamide were only 0.43 times as likely to have subjective improvement as the patients treated by castration . A comparison of pharmacologic effects showed that only the incidence of hot flushes was lower in the bicalutamide group , whereas breast tenderness and gynecomastia were more common . This difference in hot flushes , however , translated into better quality of life during the first several months with regard to sexual relations and sexual functioning . CONCLUSIONS Bicalutamide monotherapy at 50 mg/day appears inferior to castration in overall objective and subjective response rates . Whether higher doses of bicalutamide can compete more favorably will need to be tested in further clinical trials Between 1960 and 1975 , the Veterans Administration Cooperative Urological Research Group conducted a consecutive series of 3 major r and omized clinical trials comparing various endocrine treatments for newly diagnosed prostate cancer patients . Six major conclusions concerning hormonal treatment emerged from these studies : 1 ) increased hazard of cardiovascular death after therapy with 5 mg diethylstilbestrol ( DES ) ; 2 ) orchiectomy plus DES no better than orchiectomy or DES alone ; 3 ) equivalent effect of 1.0 and 5.0 mg DES on cancer ; 4 ) reduced cardiovascular hazard from therapy with 1.0 mg DES ; 5 ) Premarin and Provera no better than 1.0 mg DES at doses studied ; 6 ) decisions about hormone treatment at diagnosis dependent on patient characteristics , mainly age and Gleason grade . In this paper , these studies are review ed briefly and data are presented to support these conclusions . Some tentative treatment recommendations are proposed Patients with previously untreated category T3 to T4 Mo or Ml prostatic cancer were allocated r and omly to receive 250 mg . cyproterone acetate per day , a loading dose of 500 mg . medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks followed by 100 mg . orally twice daily , or 1 mg . diethylstilbestrol 3 times daily in a phase III trial ( protocol 30761 ) performed by the genitourinary tract cooperative group of the European Organization for Research on the Treatment of Cancer . Of 236 patients entered 210 were eligible : 75 received cyproterone acetate , 71 medroxyprogesterone acetate and 64 diethylstilbestrol .  Local and distant tumor response , time to progression , survival and toxicity were assessed 
    Output:
    
When it is feasible , quantitative meta- analysis can increase power and precision and enhance estimates of treatment effects and exposure risks .