***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: Sipuleucel‐T is an investigational active cellular immunotherapy product design ed to stimulate an immune response against prostate cancer . The safety and efficacy  of sipuleucel‐T was evaluated in 2 identically design ed , r and omized , double‐blind , placebo‐controlled trials ( D9901 and D9902A ) conducted in men with advanced prostate cancer Granulocyte macrophage colony-stimulating factor is a pleiotropic cytokine capable of inducing systemic immune responses against experimental and human tumors . To evaluate the efficacy of GM-CSF treatment in patients with hormone-refractory prostate cancer , we conducted sequential Phase II studies in 36 men with progressive disease after and rogen deprivation and anti and rogen withdrawal . In a first cohort of patients ( n = 23 ) , GM-CSF was administered s.c . at a dose of 250 microg/m2 daily for 14 days of a 28-day treatment period . After we observed oscillating prostate-specific antigen ( PSA ) responses in several patients in this first cohort , a second trial was performed in which patients ( n = 13 ) received maintenance GM-CSF ( 250 microg/m2 three times weekly ) after the first 14 days of daily GM-CSF . All patients were treated until disease progression . Response was assessed by evaluation of serial changes in serum PSA and sequential imaging studies . In cohort I , 10 of 22 patients ( 45 % ) had a PSA versus time plot with a sawtooth pattern , with PSA declining during GM-CSF therapy and climbing during the off-therapy period ; 5 patients had at least two consecutive declines in PSA , with a median response duration of 3.5 months . All but one patient in cohort II experienced a decline in PSA ( median decline , 32 % ) , but a PSA decline greater than 50 % and sustained for more than 6 weeks was seen in only one patient , who had a > 99 % decline in PSA and an improvement in bone scan lasting for 14 + months . Changes in PSA levels could not be attributed to direct or indirect effects of GM-CSF on the PSA assay or down-regulation of PSA expression by GM-CSF .  Toxicity was very mild , consisting primarily of transient constitutional symptoms and injection site reactions . These data suggest that GM-CSF may have antitumor activity in advanced prostate cancer , and the use of GM-CSF may be a confounding variable when PSA responses are used as an end point in clinical trials evaluating new regimens for the treatment of advanced prostate cancer We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma . Thirteen patients were treated with two infusions , 1 month apart , of autologous dendritic cells ( APC8015 ) preexposed ex vivo to PA2024 , a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor ( GM-CSF ) and human prostatic acid phosphatase ( PAP ) . The infusions were followed by three s.c . monthly doses of PA2024 without cells .  Three groups of patients each received PA2024 at 0.3 , 0.6 , or 1.0 mg/injection . All Ps were two-sided . Treatment was well tolerated . After infusions of APC8015 , patients experienced only mild ( grade 1 - 2 ) short-lived fever and /or chills , myalgia , pain , and fatigue . One patient developed grade 3 fatigue . Four patients developed mild local reactions to s.c . PA2024 . Twelve patients were evaluable for response to treatment . Circulating prostate-specific antigen levels dropped in three patients . T cells , drawn from patients after infusions of APC8015 , but not before , could be stimulated in vitro by GM-CSF ( P = 0.0004 ) and PAP ( P = 0.0001 ) , demonstrating broken immune tolerance against these two normal proteins . Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF . However , antibodies to GM-CSF and , to a much lesser extent , to PAP reached maximum titers only after two or even three injections of PA2024 , showing that directly injected PA2024 was involved in stimulation of humoral immunity . Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients , warranting further studies of this mode of immunotherapy 4534 Background : Sipuleucel-T is an autologous cellular immunotherapy approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant ( hormone refractory ) prostate cancer . METHODS After disease progression , subjects in the control arms of 3 r and omized controlled trials ( RCT ) of sipuleucel-T  were offered 3 infusions of APC8015F , an autologous immunotherapy made from cells cryopreserved at the time of control generation . RESULTS 165/249 ( 66.3 % ) of the control group received APC8015F .  Median time from r and omization to first APC8015F infusion was 5.2 months ( range 1.8 to 33.1 ) , and from objective disease progression to first infusion was 2.2 months ( range 0.5 to 14.6 ) . 145 subjects ( 87.9 % ) received all 3 infusions .  APC8015F-treated subjects had improved post-progression survival relative to untreated controls ( HR = 0.52 [ 95 % CI : 0.37 , 0.73 ] ; unadjusted Cox regression ; P = 0.0001 , log rank test ) , with median survival times of 20.0 and 9.8 months , respectively . APC8015F-treated subjects had more favorable prognostic features than untreated controls . To account for these differences , a Cox regression model was fit using backward selection , and included the following independent predictors of post-progression survival : lactate dehydrogenase , alkaline phosphatase , ECOG status , age , number of bone metastases , and hemoglobin . In addition , the model included post-r and omization salvage treatment and docetaxel use as time dependent covariates . This analysis revealed a positive  docetaxel effect ( HR = 0.86 [ 95 % CI : 0.60 , 1.22 ] ; P = 0.40 ) , and a positive APCF8015F treatment effect ( HR = 0.78 [ 95 % CI : 0.54 , 1.11 ] ; P = 0.17 ) . In subjects who received at least one infusion of APC8015F , the cumulative product lot release characteristics of CD54 upregulation and total nucleated cell counts were correlated with survival after salvage treatment ( p=0.03 and p=0.04 , respectively ) . CONCLUSIONS Post-progression treatment with APC8015F may have extended survival of subjects , potentially reducing the magnitude of survival difference observed between sipuleucel-T and controls in RCT PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as " new lesions " or " no new lesions , " changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T.  Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . PURPOSE The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported . PATIENTS AND METHODS R and omized clinical trials ( RCTs ) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed . Hazard ratios ( HRs ) and 95 % CIs were extracted for time-to-event end points described for each RCT . HRs were pooled for three groups : agents directed against a specific molecular target , for which the target population is selected by a biomarker ( group A ) ; less specific biologic targeted agents ( group B ) ; and chemotherapeutic agents ( group C ) . Monthly market prices  of these different drugs were compared . RESULTS For overall survival ( OS ) , the pooled HR was 0.69 ( 95 % CI , 0.59 to 0.81 ) for group A ( six drugs , six trials ) ; it was 0.78 ( 95 % CI , 0.74 to 0.83 ) for group B ( seven drugs , 14 trials ) ; and it was 0.84 ( 95 % CI , 0.79 to 0.90 ) for group C ( eight drugs , 12 trials ) . For progression-free survival ( PFS ) , the pooled HR was 0.42 ( 95 % CI , 0.36 to 0.49 ) for group A ( six drugs , seven trials ) ; it was 0.57 ( 95 % CI , 0.51 to 0.64 ) for group B ( seven drugs , 14 trials ) ; and it was 0.75 ( 95 % CI , 0.66 to 0.85 ) for group C ( six drugs , 10 trials ) . Tests for heterogeneity between subgroups were highly significant for PFS ( P < .001 ) and OS ( P = .02 ) . The median monthly prices for st and ard doses of drugs were $ 5375 for group A , $ 5644 for group B , and $ 6584 
    Output:
    
The addition of sipuleucel-T , an immunotherapeutic agent , to the armamentarium represents a paradigm shift in therapy for mCRPC .