***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: Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma ( ARCC ) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus ( Torisel ™ ) or interferon-α ( IFN ) .  Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN ( 3 million units [ MU ] subcutaneously three times weekly , escalating to 18 MU ) or temsirolimus ( 25 mg intravenously weekly ) . Results Approximately 80 % of patients had clear cell and 20 % of patients had other histologies , the majority of which were papillary . Patients with clear cell and other RCC histologies , treated with temsirolimus , demonstrated comparable median overall and progression-free survival . In contrast , patients with other RCC histologies , treated with IFN , demonstrated shorter median overall and progression-free survival than patients with clear cell RCC . Hazard ratios for death for treatment with temsirolimus versus IFN were less than 1 for patients regardless of tumor histology . For patients treated with temsirolimus , 59 % with clear cell and 68 % with other RCC histologies experienced tumor reductions . For patients treated with IFN , 35 % with clear cell and 14 % with other RCC histologies had tumor reductions . However , temsirolimus did not appear to improve the objective response rate compared to IFN . Temsirolimus result ed in a superior clinical benefit rate compared with IFN , regardless of tumor histology . Conclusion Temsirolimus appears to be efficacious in patients with clear cell and non-clear cell histologies and can , therefore , be used for the treatment of all types of RCC PURPOSE Mature survival data and evaluation of vascular endothelial growth factor ( VEGF ) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial ( TARGET ) study in patients with renal cell carcinoma ( RCC ) are reported . PATIENTS AND METHODS Nine hundred three previously treated patients were r and omly assigned to receive sorafenib versus placebo . On demonstration of progression-free survival ( PFS ) benefit with sorafenib , patients assigned to placebo were offered sorafenib .  Overall survival ( OS ) was determined at two planned interim analyses and one final analysis , with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib . The relationships between baseline VEGF level and prognosis and efficacy were evaluated . RESULTS The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo ( 17.8 v 15.2 months , respectively ; hazard ratio [ HR ] = 0.88 ; P = .146 ) ; however , when post-cross-over placebo survival data were censored , the difference became significant ( 17.8 v 14.3 months , respectively ; HR = 0.78 ; P = .029 ) . Adverse events at 16 months after cross over were similar to those previously reported . Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status ( P < .0001 ) , Memorial Sloan-Kettering Cancer Center score ( P < .0001 ) , and PFS and OS in univariate ( PFS , P = .0013 ; OS , P = .0009 ) and multivariate ( PFS , P = .0231 ; OS , P = .0416 ) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib ( P = .0145 ) . Both high-VEGF ( P < .01 ) and low-VEGF ( P < .01 ) groups benefited from sorafenib . CONCLUSION Although an OS benefit was not seen on a primary intent-to-treat analysis , results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib , suggesting an important cross-over effect . VEGF levels are prognostic for PFS and OS in RCC . The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability .  Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) PURPOSE To assess the disease-stabilizing activity of carboxyaminoimidazole ( CAI ) in patients with metastatic renal cell cancer ( RCC ) using a r and omized discontinuation trial ( RDT ) design . PATIENTS AND METHODS Recruited patients had a performance status of 0 to 2 , minimal neuropathy or cerebellar dysfunction , measurable disease , and normal organ function . Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response . Protocol treatment was discontinued for unacceptable toxicity or progressive disease ;  patients with stable disease at the 16-week evaluation point were r and omly assigned in a double-blind manner to continued CAI or placebo . The primary end point was the stable disease rate in the r and omized groups . RESULTS A total of 368 patients were accrued and received therapy . Ninety percent had a performance status of 0 or 1 , 80 % underwent a prior nephrectomy , and 41 % had received no prior systemic therapy .  Serious or life-threatening toxicity was experienced by 34 % , with asthenia ( 15 % ) and neuropsychiatric difficulties ( 7 % ) being most common . At the r and omization point , 51 % of patients had progressed , 30 % withdrew , 1 % experienced a partial response , and 17 % had stable disease and were r and omly assigned . A Bayesian futility analysis utilizing the first 49 r and omly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9 % even under the most optimistic a priori assumptions , and further trial accrual was halted . CONCLUSION CAI is inactive in RCC . The RDT design should be further explored for evaluating activity of putative disease stabilizing agents 5032 Background : AV-951 is a potent inhibitor of VEGFR-1 , 2 & 3 kinases ( IC50 0.21 , 0.16 and 0.24 nM respectively ) , and inhibits cKit and PDGFR at 10-times higher concentrations ( IC50 1.63 and 1.72 nM respectively ) . In a phase II RDT of AV-951 ( 1.5 mg/day ; 3 wks on , 1 wk off ) in RCC , preliminary ORR at wk 16 was 28 % ( ASCO GU . 2008 ; abstract # 283 ) . METHODS Pts with locally advanced or metastatic RCC ( any histology ) and no prior VEGF-targeted therapy received AV-951 for 16 wks , after which further treatment was assigned based on response . Pts with ≥ 25 % tumor shrinkage continued treatment with AV-951 , while pts with < 25 % change from baseline were r and omly assigned to receive AV-951 or placebo for 12 wks ( double-blinded ) . The primary end points were ( 1 ) objective response rate ( ORR ) at 16 wks , ( 2 ) percentage of r and omly assigned pts remaining progression free at 12 wks following r and omization , ( 3 ) safety profile . RESULTS 272 pts were enrolled : 70 % male , 93 % white , median age 56 yrs . 53 % pts were treatement naïve , 72 % had undergone nephrectomy and 83 % had RCC with clear cell component . With a median duration of treatment of 5 mo ( range 0 - 12 mo ) , the investigator assessed ORR ( CR+PR ) is 27.2 % ( 30 % in clear cell RCC ) , SD 60.5 % and Disease Control Rate ( CR/PR + SD ) 88 % . 118 ( 43 % ) pts were r and omized to AV-951 or placebo . The most common treatment-related AEs ( all grade s ) were hypertension ( HTN , 42 % ) and dysphonia ( 16 % ) . Guidelines for management of HTN were provided to investigators , and 52 % pts received anti-hypertensives . Minimal ( all grade s ) diarrhea ( 9 % ) , fatigue ( 8 % ) , stomatitis ( 3 % ) and h and -foot syndrome ( 2 % ) were observed . Laboratory abnormalities ( all grade s ) were notable for minimal neutropenia ( 8 % ) and elevations of AST ( 21 % ) and ALT ( 21 % ) . AEs led to dose reduction in 4 % and treatment discontinuation in 5.5 % of pts . CONCLUSIONS Interim results of this phase II study demonstrate that AV-951 is active in RCC . The AE profile of AV-951 is consistent with that of a selective VEGFR inhibitor , with minimal off-target toxicities . Up date d results of ORR ( including independent radiology assessment ) , safety , percentage of r and omly assigned pts remaining progression free at 12 wks , and overall PFS will be presented . [ Table : see text ] 4550 Background : Tivozanib is a potent and selective small molecule tyrosine kinase inhibitor ( TKI ) of VEGFR-1 , -2 , and -3 . METHODS Patients ( pts ) with advanced RCC ( all histologies ) and no prior VEGF-targeted therapy were enrolled . All pts received 16 wks of open-label tivozanib 1.5 mg/d , following which pts were stratified : pts with ≥25 % tumor shrinkage continued tivozanib , pts with ≥25 % tumor increase were discontinued , and pts with < 25 % tumor change from baseline ( SD ) were r and omized to 12 wks of double-blind ( DB ) tivozanib or placebo ; r and omized pts were un-blinded at the time of progressive disease ( PD ) or at the end of the DB phase , and those on placebo were allowed to restart tivozanib . CT scans were read by blinded , independent review ers . RESULTS 272 pts were enrolled : 83 % had clear cell RCC , 73 % had undergone nephrectomy , and 46 % had received prior therapy . In the overall study population , 84 % of pts demonstrated PR or SD by Week 16 . In the overall population , the ORR was 30 % , DCR was 85 % and median PFS 11.7 mo . Pts with clear cell histology who had undergone a nephrectomy demonstrated the highest efficacy , with an ORR of 36 % , DCR of 88 % and median PFS of 14.8 mo . Hypertension ( 45 % ) and dysphonia ( 22 % ) were the most common drug-related AEs of any grade . There was a low incidence of drug-related diarrhea ( 12 % ) , asthenia ( 10 % ) , fatigue ( 8 % ) , dyspnea ( 6 % ) , cough ( 5 % ) , anorexia ( 5 % ) , stomatitis ( 4 % ) , h and -foot syndrome ( 4 % ) and proteinuria ( 3 % ) . Grade 3/4 AEs were infrequent ; the most common grade 3/4 AE was hypert 
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In treatment-naive patients with mostly good-moderate prognostic risk , in separate trials oral sunitinib ( one trial ) and intravenous BEV plus subcutaneousinterferon-α ( two trials ) improved PFS compared with the previous st and ard of care interferon-α within r and omised phase III trials .
Sorafenib did not improve PFS over interferon-α in the first-line setting and the addition of cytokines did not improve sorafenib efficacy .
In poor-risk patients , the mTOR inhibitor temsirolimus  improved PFS and overall survival ( OS ) .
A more substantial effect on OS may have been diluted by crossover from control therapy to the investigational arm and /or by other anti-angiogenic agents after trial closure .
A clear cell RCC ( ccRCC ) component was required for most trials , and information for non-ccRCCs is consequently limited CONCLUSIONS Agents targeting VEGF and mTOR pathways improve PFS in both first-line and second-line setting s. These treatments rarely yield complete responses and thus are not curative .
No placebo-controlled trial has reported a health-related quality of life benefit