***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 : To evaluate the efficacy and tolerability of the urokinase plasminogen activator ( uPA ) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma ( LAPC ) . Methods : Within a prospect i ve multicenter study , LAPC patients were r and omly assigned to receive 1000 mg m−2 of gemcitabine IV weekly either alone ( arm A ) or in combination with 200 mg ( arm B ) or 400 mg ( arm C ) oral upamostat daily . Efficacy endpoints of this proof-of-concept study included response rate , time to first metastasis , progression-free and overall survival ( OS ) . Results : Of the 95 enroled patients , 85 were evaluable for response and 93 for safety . Median OS was 12.5 months ( 95 % CI 8.2–18.2 ) in arm C , 9.7 months ( 95 % CI 8.4–17.1 ) in arm B and 9.9 months ( 95 % CI 7.4–12.1 ) in arm A ; corresponding 1-year survival rates were 50.6 % , 40.7 % and 33.9 % , respectively . More patients achieved a partial remission ( confirmed responses by RECIST ) with upamostat combination therapy ( arm C : 12.9 % ; arm B : 7.1 % ; arm A : 3.8 % ) . Overall , only 12 patients progressed by developing detectable distant metastasis ( arm A : 4 , arm B : 6 , arm C : 2 ) . The most common adverse events considered to be related to upamostat  were asthenia , fever and nausea . Conclusion : In this proof-of-concept study targeting the uPA system in LAPC , the addition of upamostat to gemcitabine was tolerated well ; similar survival results were observed for the three treatment arms Gemcitabine is a key drug for the treatment of pancreatic cancer ; however , with its limitation in clinical benefits , the development of another potent therapeutic is necessary . Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis , and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide ( elpamotide ) . Based on the promising results of this phase I trial , a multicenter , r and omized , placebo‐controlled , double‐blind phase II/III clinical trial has been carried out for pancreatic cancer . The eligibility criteria included locally advanced or metastatic pancreatic cancer . Patients were assigned to either the Active group ( elpamotide + gemcitabine ) or Placebo group ( placebo + gemcitabine ) in a 2:1 ratio by the dynamic allocation method . The primary endpoint was overall survival . The Harrington – Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately . A total of 153 patients ( Active group , n = 100 ; Placebo group , n = 53 ) were included in the analysis . No statistically significant differences were found between the two groups in the prolongation of overall survival ( Harrington – Fleming P‐value , 0.918 ; log – rank P‐value , 0.897 ; hazard ratio , 0.87 , 95 % confidence interval [ CI ] , 0.486–1.557 ) . Median survival time was 8.36 months ( 95 % CI , 7.46–10.18 ) for the Active group and 8.54 months ( 95 % CI , 7.33–10.84 ) for the Placebo group . The toxicity observed in both groups was manageable . Combination therapy of elpamotide with gemcitabine was well tolerated . Despite the lack of benefit in overall survival , subgroup analysis suggested that the patients who experienced severe injection site reaction , such as ulceration and erosion , might have better survival Abstract Background Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis . A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine . The present r and omized , double-blinded , phase II trial compared the efficacy and safety of gemcitabine plus simvastatin ( GS ) with those of gemcitabine plus placebo ( GP ) in patients with locally advanced and metastatic pancreatic cancer . Methods Patients were r and omly assigned to receive a 3-week regimen with GS ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus simvastatin 40 mg once daily ) or GP ( gemcitabine 1,000 mg/m2 on days 1 , 8 , and 15 plus placebo ) . The primary end point was time to progression ( TTP ) . Results Between December 2008 and April 2012 , 114 patients were enrolled .  The median TTP was not significantly different between the two arms , being 2.4 months ( 95 % CI 0.7–4.1 months ) and 3.6 months ( 95 % CI 3.1–4.1 months ) in the GS and GP arms , respectively ( P = 0.903 ) . The overall disease control rate was 39.7 % ( 95 % CI 12.2–33.8 % ) and 57.1 % ( 95 % CI 19.8–44.2 % ) in the GS and GP arms , respectively ( P = 0.09 ) . The 1-year expected survival rates were similar ( 27.7 and 31.7 % in the GS and GP arms , respectively ; P = 0.654 ) . Occurrence of grade 3 or 4 adverse events was similar in both arms , and no patients had rhabdomyolysis . Conclusions Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit , although it also does not result in increased toxicity . Given the emerging role of statins in overcoming resistance to anti-EGFR treatment , further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents , such as erlotinib or cetuximab , plus gemcitabine for treating advanced pancreatic cancer BACKGROUND Axitinib ( AG-013736 ) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , which have an important role in pancreatic cancer . The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone . METHODS Between January and August , 2006 , 103 patients with unresectable , locally advanced , or metastatic pancreatic cancer were r and omly assigned in a two to one ratio to receive gemcitabine ( 1000 mg/m(2 ) ) plus axitinib 5 mg twice daily ( n=69 ) or gemcitabine ( 1000 mg/m(2 ) ) alone ( n=34 ) by a central ised registration system . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00219557 . FINDINGS All r and omised patients were included in the efficacy analyses . Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone ( 6.9 [ 95 % CI 5.3 - 10.1 ] months vs 5.6 [ 3.9 - 8.8 ] months ) . The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone , adjusted for stratification factors , was 0.71 ( 95 % CI 0.44 - 1.13 ) . The most common grade 3 or worse adverse events were fatigue ( 15 [ 22 % ] patients in the gemcitabine plus axitinib group vs one [ 3 % ] in the gemcitabine alone group ) , abdominal pain ( eight [ 12 % ] vs five [ 16 % ] ) , and asthenia ( eight [ 12 % ] vs one [ 3 % ] ) . INTERPRETATION Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone ; the small , non-statistically significant gain in overall survival needs to be assessed in a r and omised phase III trial BACKGROUND Axitinib is a potent , selective inhibitor of vascular endothelial growth factor ( VEGF ) receptors 1 , 2 , and 3 . A r and omised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients . On the basis of these results , we aim ed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial . METHODS In this double-blind , placebo-controlled , phase 3 study , eligible patients had metastatic or locally advanced pancreatic adenocarcinoma , no uncontrolled hypertension or venous thrombosis , and Eastern Cooperative Oncology Group performance status 0 or 1 . Patients , stratified by disease extent ( metastatic vs locally advanced ) , were r and omly assigned ( 1:1 ) to receive gemcitabine 1000 mg/m(2 ) intravenously on days 1 , 8 , and 15 every 28 days plus either axitinib or placebo . Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day , which could be dose-titrated up to 10 mg twice daily if well tolerated . A central ised r and omisation procedure was used to assign patients to each treatment group , with r and omised permuted blocks within strata . Patients , investigators , and the trial sponsor were masked to treatment assignments . The primary endpoint was overall survival . All efficacy analyses were done in all patients assigned to treatment groups for whom data were available ; safety and treatment administration and compliance assessment s were based on treatment received . This study is registered at Clinical Trials.gov , number NCT00471146 . FINDINGS Between July 27 , 2007 , and Oct 31 , 2008 , 632 patients were enrolled and assigned to treatment groups  ( 316 axitinib , 316 placebo ) . At an interim analysis in January , 2009 , the independent data monitoring committee concluded that the futility boundary had been crossed . Median overall survival was 8·5 months ( 95 % CI 6·9 - 9·5 ) for gemcitabine plus axitinib ( n=314 , data missing for two patients ) and 8·3 months ( 6·9 - 10·3 ) for gemcitabine plus placebo ( n=316 ; hazard ratio 1·014 , 95 % CI 0·786 - 1·309 ; one-sided p=0·5436 ) . The most common grade 3 or higher adverse events  for gemcitabine plus axitinib and gemcitabine plus placebo were hypertension ( 20 [ 7 % ] and 5 [ 2 % ] events , respectively ) , abdominal pain ( 20 [ 7 % ] and 17 [ 6 % ] ) , fatigue ( 27 [ 9 % ] and 21 [ 7 % ] ) , and anorexia ( 19 [ 6 % ] and 11 [ 4 % ] ) . INTERPRETATION The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer . These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease . FUNDING Pfizer BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine  ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine  ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months 
    Output:
    
The use of molecular targeted agents does not translate into clinical benefit .