***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 To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma ( RCC ) treated with interferon-alfa as initial systemic therapy . The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy . PATIENTS AND METHODS Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospect i ve clinical trials were the subjects of this retrospective analysis . Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model . RESULTS The median overall survival time was 13 months . The median time to progression was 4.7 months . Five variables were used as risk factors for short survival : low Karnofsky performance status , high lactate dehydrogenase , low serum hemoglobin , high corrected serum calcium , and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year . Each patient was assigned to one of three risk groups : those with zero risk factors ( favorable risk ) , those with one or two ( intermediate risk ) , and those with three or more ( poor risk ) . The median time to death of patients deemed favorable risk was 30 months . Median survival time in the intermediate-risk group was 14 months . In contrast , the poor-risk group had a median survival time of 5 months . CONCLUSION Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations . The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma ( nccRCC ) . PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes . Patients were treated with 50 mg/day oral sunitinib for 4 weeks , followed by 2 weeks of rest . The primary end point was overall response rate ( RR ) . RESULTS Thirty-one eligible patients were enrolled . Twenty-four patients ( 77 % ) had prior nephrectomy . By Memorial Sloan-Kettering Cancer Center criteria , 8 patients ( 26 % ) had poor risk and 14 ( 45 % ) had intermediate risk . Twenty-two patients had papillary renal cell carcinoma ( RCC ) , and three had chromophobe RCC . Eleven patients had partial response with a RR of 36 % ( 95 % confidence interval ( CI ) 19 % to 52 % ) and an additional 17 patients ( 55 % ) had stable disease . Median duration of response was 12.7 months ( 95 % CI 6.3 - 19.1 months ) , and median progression-free survival was 6.4 months ( 95 % CI 4.2 - 8.6 months ) . At a median follow-up duration of 18.7 months ( 95 % CI 13.7 - 23.7 months ) , 13 patients ( 42 % ) had died , result ing in an estimated median survival of 25.6 months ( 95 % CI 8.4 - 42.9 months ) . Toxicity profiles were commensurate with prior reports . CONCLUSIONS Sunitinib has promising activity in patients with nccRCC ( NCT01219751 ) 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 ] . ) STUDY OBJECTIVE To quantify the influence of a high-fat meal on the oral bioavailability of the immunosuppressant  everolimus in a single-dose study in healthy subjects and to confirm the results in a small food-effect screening assessment in patients with renal transplants who were receiving multiple-dose everolimus .  DESIGN R and omized , open-label , crossover , single-dose study and confirmatory screening . SETTING Phase 1 unit for the single-dose study and two German hospitals for the patient screening . SUBJECTS Twenty-four healthy male volunteers ; six clinical ly stable patients with renal transplants who were originally part of a phase I dose-escalation study . INTERVENTION The 24 healthy men received everolimus 2 mg orally under fasting conditions and after a high-fat meal . The six patients received everolimus 2.5 mg/day orally , in addition to cyclosporine and prednisone . On two occasions , a pharmacokinetic profile was obtained over the dosing interval after drug administration under fasting conditions and after a high-fat meal in a r and omized sequence . MEASUREMENTS AND MAIN RESULTS In the single-dose study in healthy subjects , a high-fat meal delayed everolimus time to maximum concentration ( Tmax ) by a median 1.25 hours , reduced peak blood concentration ( Cmax ) by 60 % , and reduced area under the concentration-time curve ( AUC ) by 16 % . In the multiple-dose screening in patients with renal transplants , a high-fat meal delayed Tmax by a median 1.75 hours and reduced Cmax by 53 % and AUC by 21 % . Everolimus trough levels showed no food effect , whereas the peak-trough fluctuation was dampened by 52 % . CONCLUSIONS A high-fat meal modestly reduced everolimus AUC . To minimize longitudinal variability in exposure , everolimus should be administered consistently either with food or without food To assess the response rate and safety of sorafenib in different sub population s of patients with advanced renal cell carcinoma ( RCC ) BACKGROUND Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies . PATIENTS AND METHODS PREDICT ( Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib ) was a prospect i ve , noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries . Patient characteristics , therapy duration , tumor status , and tolerability  were assessed at baseline and during routine follow-up . RESULTS Overall , 2599 patients were evaluable for safety and 2311 for efficacy . The diverse population included patients with brain metastases ( 5 % ) , non-clear-cell histologies ( 17 % ) , high Memorial Sloan-Kettering Cancer Center risk score ( 11 % ) , poor Eastern Cooperative Oncology Group performance status ( PS ≥ 2 , 29 % ) , and patients with no previous nephrectomy ( 16 % ) or no previous systemic therapy ( 37 % ) .  The median duration of sorafenib  therapy was 7.3 months and was similar in clinical ly relevant subgroups ( eg , patients with PS 2 , brain metastases , or concomitant hypertension or diabetes [ range , 6.7 - 7.0 months ] ) . The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies ( 4.6 and 4.8 months , respectively ) . The most common drug-related adverse events were h and -foot skin reaction ( 20 % ) , diarrhea ( 17 % ) , and rash ( 8 % ) . CONCLUSION Sorafenib was generally well tolerated and provided clinical benefit in a large , diverse population of patients with advanced RCC treated in routine clinical practice OBJECTIVE Temsirolimus , an inhibitor of the mammalian target of rapamycin , is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe .  Temsirolimus was not yet evaluated in East Asian patients . METHODS This non-r and omized Phase II study enrolled 82 patients with advanced renal cell carcinoma [ 20 ( 24 % ) Japanese , 30 ( 37 % ) Korean and 32 ( 39 % ) Chinese patients ; median age ( range ) : 55 ( 26 - 83 ) years ] . Most ( 71 % ) received prior systemic therapy for metastatic disease ; two-thirds were intermediate risk . Six Japanese patients received  intravenous temsirolimus 20 mg/m(2 ) weekly for tolerability assessment ( Group A ) ; the remaining 76 received a 25 mg flat dose weekly ( Group B ) . Temsirolimus was dosed once weekly . Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population . RESULTS In the entire population , regardless of treatment group , the clinical benefit rate was 48 % ( 95 % confidence interval : 36 , 59 ) . Objective response rate was 11 % ( 95 % confidence interval : 5 , 20 ) , median progression-free survival was 7.3 months ( 95 % confidence interval : 4.0 , 9.2 ) and median time to treatment failure was 5.4 months ( 95 % confidence interval : 3.5 , 7.4 ) . No patient in Group A demonstrated dose-limiting toxicity . The most frequent Grade 3 or 4 drug-related adverse events were anemia , hyperglycemia , hypophosphatemia and stomatitis ( 5 % each ) . Serious adverse events reported in ≥ 5 % of patients were pneumonia ( 9 % ) and interstitial lung disease ( 7 % ) . Temsirolimus and its major metabolite , sirolimus , were long-lived throughout the dosage interval , with no evidence of accumulation . CONCLUSION Temsirolimus was well tolerated and showed promising activity in Japanese , Korean and Chinese patients with advanced renal cell carcinoma PURPOSE Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma ( RCC ) treatment , when given by the st and ard intermittent schedule as well as a continuous daily dosing ( CDD ) schedule . A trial was conducted to compare the schedules . PATIENTS AND METHODS Patients with treatment-naive , clear cell advanced RCC were r and omly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment ( schedule 4/2 ; n = 146 ) or 37.5 mg/d on the CDD schedule ( n = 146 ) for up to 2 years . The primary end point was time to tumor progression . RESULTS Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule ( hazard ratio , 0.77 ; 95 % CI , 0.57 to 1.04 ; P = .090 ) . No significant difference was observed in overall survival ( 23.1 v 23.5 months ; P = .615 ) , commonly reported adverse events , or patient-reported kidney cancer symptoms . Schedule 4/2 was statistically superior to CDD in time to deterioration , a composite end point of death , progression , and disease-related symptoms ( P = .034 ) . CONCLUSION ; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2 . Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2 , adherence to this dose 
    Output:
    
Temsirolimus increases progression-free survival and overall survival compared to  IFN-alpha .
Discussion Experts tend to prefer  sunitinib  as first-line therapy even in poor-prognosis mRCC .
In light of the systematic review , no targeted therapy appears to be more effective than another .