***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 plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily  and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone A multicenter phase I clinical trial of RP 56976 ( docetaxel )  , a new anticancer drug , was performed with single and repeated doses . Based on the results of phase I clinical trials conducted in the United States and Europe , the starting dose was 10 mg/m2 . The dose was subsequently increased to 20 , 50 , 70 and 90 mg/m2 . A dose of 60 mg/m2 was additionally tested . Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour . Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner . The dose limiting factor ( DLF ) of docetaxel is leukopenia ( especially , neutropenia ) . Based on the observation of the DLF , the maximum tolerated dose ( MTD ) was determined to be 70 - 90 mg/m2 . The white blood cell count reached a nadir about 9.5 - 19.5 days ( median ) after administration , and took 7 - 11 days ( median ) to recover . Other adverse reactions observed were nausea/vomiting anorexia , alopecia , diarrhea , fatigue and fever , which were all acceptable . The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial BACKGROUND Docetaxel administered every 3 weeks is a st and ard treatment for castration-resistant advanced prostate cancer . We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer , and did a prospect i ve , multicentre , r and omised , phase 3 study to compare efficacy and safety . METHODS Eligible patients had advanced prostate cancer ( metastasis , a prostate-specific-antigen test result of more than 10·0 ng/mL , and WHO performance status score of 0 - 2 ) , had received no chemotherapy ( except with estramustine ) , had undergone surgical or chemical castration , and had been referred to a treatment centre in Finl and , Irel and , or Sweden . Enrolment and treatment were done between March 1 , 2004 , and May 31 , 2009 . R and omisation was done central ly and stratified by centre and WHO performance status score of 0 - 1 vs 2 . Patients were assigned 75 mg/m(2 ) docetaxel intravenously on day 1 of a 3-week cycle , or 50 mg/m(2 ) docetaxel intravenously on days 1 and 15 of a 4-week cycle . 10 mg oral prednisolone was administered daily to all patients . The primary endpoint was time to treatment failure ( TTTF ) . We assessed data in the per- protocol population . This study is registered with Clinical Trials.gov , number NCT00255606 . FINDINGS 177 patients were r and omly assigned to the 2-weekly docetaxel  group and 184 to the 3-weekly group . 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis . The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration ( 5·6 months , 95 % CI 5·0 - 6·2 vs 4·9 months , 4·5 - 5·4 ; hazard ratio 1·3 , 95 % CI 1·1 - 1·6 , p=0·014 ) . Grade 3 - 4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group , including neutropenia ( 93 [ 53 % ] vs 61 [ 36 % ] ) , leucopenia ( 51 [ 29 % ] vs 22 [ 13 % ] ) , and febrile neutropenia ( 25 [ 14 % ] vs six [ 4 % ] ) . Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks ( 43 [ 24 % ] vs 11 [ 6 % ] , p=0·002 ) . INTERPRETATION Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated . FUNDING Sanofi Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer  , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . Recent insights into the regulation of the and rogen receptor ( AR ) activity led to novel therapeutic targeting of AR function in prostate cancer patients .  Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer ; however , the mechanism underlying the action of this tubulin-targeting drug is not fully understood . This study investigates the contribution of microtubules and the cytoskeleton to and rogen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer . Tissue microarrays from  docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen ( PSA ) and AR immunoreactivity . The AR transcriptional activity was determined in prostate cancer cells in vitro , based on PSA mRNA expression and the and rogen response element reporter activity . The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence . Treatment of prostate cancer patients  with docetaxel led to a significant translocation of AR . In untreated specimens , 50 % prostate tumor cells exhibited nuclear accumulation of AR , compared with docetaxel-treated tumors that had significantly depleted nuclear AR ( 38 % ) , paralleled by an increase in cytosolic AR . AR nuclear localization correlated with PSA expression . In vitro , exposure of prostate cancer cells to paclitaxel ( 1 μmol/L ) or nocodazole ( 5 μg/mL ) inhibited and rogen-dependent AR nuclear translocation by targeting AR association with tubulin . Introduction of a truncated AR indicated the requirement of the NH(2)-terminal domain for AR-tubulin interaction . Our findings show that in addition to blocking cell division , docetaxel impairs AR signaling , evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer 
    Output:
    
Compared to ADT alone , the early ( within 120 days of beginning ADT ) addition of taxane-based chemotherapy to ADT for hormone-sensitive prostate cancer probably prolongs both overall and disease-specific survival and delays disease progression .
There may be an increase in toxicity with taxane-based chemotherapy in combination with ADT .