***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 Pre clinical and preliminary clinical data indicate that ch14.18 , a monoclonal antibody against the tumor-associated disialoganglioside GD2 , has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or interleukin-2 . We conducted a study to determine whether adding ch14.18 , GM-CSF , and interleukin-2 to st and ard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma . METHODS Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were r and omly assigned , in a 1:1 ratio , to receive st and ard therapy ( six cycles of isotretinoin ) or immunotherapy ( six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2 ) . Event-free survival and overall survival were compared between the immunotherapy group and the st and ard-therapy group , on an intention-to-treat basis . RESULTS A total of 226 eligible patients were r and omly assigned to a treatment group . In the immunotherapy group , a total of 52 % of patients had pain of grade 3 , 4 , or 5 , and 23 % and 25 % of patients had capillary leak syndrome and hypersensitivity reactions , respectively . With 61 % of the number of expected events observed , the study met the criteria for early stopping owing to efficacy . The median duration of follow-up was 2.1 years . Immunotherapy was superior to st and ard therapy with regard to rates of event-free survival ( 66±5 % vs. 46±5 % at 2 years , P=0.01 ) and overall survival ( 86±4 % vs. 75±5 % at 2 years , P=0.02 without adjustment for interim analyses ) . CONCLUSIONS Immunotherapy with ch14.18 , GM-CSF , and interleukin-2 was associated with a significantly improved outcome as compared with st and ard therapy in patients with high-risk neuroblastoma . ( Funded by the National Institutes of Health and the Food and Drug Administration ; Clinical Trials.gov number , NCT00026312 . Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis . RNASEL at chromosome 1q25 encodes ribonuclease L , part of the interferon-mediated immune response to viral infection . We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospect i ve Physicians ' Health Study . Eleven single-nucleotide polymorphisms ( SNPs ) were selected using the web-based ' Tagger ' in the HapMap CEPH panel ( Utah residents of Northern and Western European Ancestry ) . Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage ( T(3)/T(4 ) , T(0)-T(4)/M(1 ) and lethal disease ) and high Gleason grade ( > /=7 ) prostate cancer . Further analyses were stratified by calendar year of diagnosis . Cox proportional hazards models examined the relationship between genotype and prostate cancer-specific survival . We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) and tumor necrosis factor-alpha receptor 2 using linear regression . Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [ AA versus GG ; odds ratio ( OR ) : 1.63 , 95 % confidence interval ( CI ) : 1.18 - 2.25 ) , and more specifically , high- grade tumors ( OR : 1.90 , 95 % CI : 1.25 - 2.89 ) . The same genotype was associated with increased CRP ( P = 0.02 ) and IL-6 ( P = 0.05 ) levels . Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era . There were no significant associations with survival . The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation . These novel findings warrant replication in future studies BACKGROUND This first-in-human phase I/IIA study was design ed to evaluate the safety and pharmacokinetics ( PKs ) of AGS-PSCA a fully human monoclonal antibody directed to prostate stem cell antigen ( PSCA ) in progressive castration-resistant prostate cancer . PATIENTS AND METHODS Twenty-nine patients were administered infusions of AGS-PSCA  ( 1 - 40 mg/kg ) every 3 weeks for 12 weeks ; 18 final patients received a 40-mg/kg loading dose followed by 20-mg/kg repeat doses . Primary end points were safety and PK . Immunogenicity , antitumor activity and circulating tumor cells were also evaluated . RESULTS No drug-related serious adverse events were noted . Dose escalation stopped before reaching the maximum tolerated dose as target concentrations were achieved . Drug levels accumulated linearly with dose and the mean terminal half-life was 2 - 3 weeks across dose levels . The 40-mg/kg loading dose followed by repeated 20-mg/kg doses yielded serum drug concentrations above the projected minimum therapeutic threshold after two to three doses without excessive drug accumulation or toxicity . Significant antitumor effects were not seen . CONCLUSIONS A 40-mg/kg loading dose followed by 20-mg/kg infusions every 3 weeks is the recommended phase II dose of AGS-PSCA . PSCA is a promising drug target and studies in prostate and other relevant solid tumors are planned PURPOSE To determine the maximum tolerated dose ( MTD ) , toxicity , human anti-J591 response , pharmacokinetics ( PK ) , organ dosimetry , targeting , and biologic activity of (177)Lutetium-labeled anti-prostate-specific membrane antigen ( PSMA ) monoclonal antibody J591 ( (177)Lu-J591 ) in patients with and rogen-independent prostate cancer ( PC ) . PATIENTS AND METHODS Thirty-five patients with progressing and rogen-independent PC received (177)Lu-J591 . All patients underwent (177)Lu-J591 imaging , PK , and biodistribution determinations . Patients were eligible for up to three retreatments . RESULTS Thirty-five patients received (177)Lu-J591 , of whom 16 received up to three doses . Myelosuppression was dose limiting at 75 mCi/m(2 ) , and the 70-mCi/m(2 ) dose level was determined to be the single-dose MTD . Repeat dosing at 45 to 60 mCi/m(2 ) was associated with dose-limiting myelosuppression ; however , up to three doses of 30 mCi/m(2 ) could be safely administered . Nonhematologic toxicity was not dose limiting . Targeting of all known sites of bone and soft tissue metastases was seen in all 30 patients with positive bone , computed tomography , or magnetic resonance images . No patient developed a human anti-J591 antibody response to deimmunized J591 regardless of number of doses . Biologic activity was seen with four patients experiencing > or= 50 % declines in prostate-specific antigen ( PSA ) levels lasting from 3 + to 8 months . An additional 16 patients ( 46 % ) experienced PSA stabilization for a median of 60 days ( range , 1 to 21 + months ) . CONCLUSION The MTD of (177)Lu-J591 is 70 mCi/m(2 ) . Multiple doses of 30 mCi/m(2 ) are well tolerated . Acceptable toxicity , excellent targeting of known sites of PC metastases , and biologic activity in patients with and rogen-independent PC warrant further investigation PURPOSE To compare single-agent gemtuzumab ozogamicin ( GO ) with best supportive care ( BSC ) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy . PATIENTS AND METHODS In this trial , patients at least 61 years old were central ly r and omized ( 1:1 ) to receive either a single induction course of GO ( 6 mg/m(2 ) on day 1 and 3 mg/m(2 ) on day 8) or BSC .  Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m(2 ) . R and omization was stratified by age , WHO performance score , CD33 expression status , and center . The primary end point was overall survival ( OS ) by intention-to-treat analysis . RESULTS A total of 237 patients were r and omly assigned ( 118 to GO and 119 to BSC ) . The median OS was 4.9 months ( 95 % CI , 4.2 to 6.8 months ) in the GO group and 3.6 months ( 95 % CI , 2.6 to 4.2 months ) in the BSC group ( hazard ratio , 0.69 ; 95 % CI , 0.53 to 0.90 ; P = .005 ) ; the 1-year OS rate was 24.3 % with GO and 9.7 % with BSC . The OS benefit with GO was consistent across most subgroups , and was especially apparent in patients with high CD33 expression status , in those with favorable/intermediate cytogenetic risk profile , and in women . Overall , complete remission ( CR [ complete remission ] + CRi [ CR with incomplete recovery of peripheral blood counts ] ) occurred in 30 of 111 ( 27 % ) GO recipients . The rates of serious adverse events ( AEs ) were similar in the two groups , and no excess mortality from AEs was observed with GO . CONCLUSION First-line monotherapy with low-dose GO , as compared with BSC , significantly improved OS  in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy . No unexpected AEs were identified and toxicity was manageable 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 To determine the maximum-tolerated dose ( MTD ) , toxicity , human antihuman antibody ( HAHA ) response , pharmacokinetics , organ dosimetry , targeting , and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ( (90)Y-J591 ) in patients with and rogen-independent prostate cancer ( 
    Output:
    
In general , results of this systematic review show promising advances in the treatment of prostate cancer patients with monoclonal antibodies against prostate-specific antigens with regard to PSA/disease response .
Conclusion Currently , the role of immunotherapy in the treatment of advanced prostate cancer still remains debated .