***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 V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy  , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib  prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC V and etanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 , epidermal growth factor receptor , and the rearranged-during-transfection oncogene . A phase I trial was conducted to describe the pharmacokinetics of v and etanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs ( EIAEDs ) and to identify the maximum tolerated dose ( MTD ) in this population . A phase II trial evaluated the efficacy of v and etanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival ( PFS6 ) . In the phase I trial , 15 patients were treated with v and etanib at doses of 300 , 400 , and 500 mg/day , in a st and ard dose-escalation design . The MTD in patients on EIAEDs was 400 mg/day , and steady-state levels were similar to those measured in patients not on EIAEDs . Dose-limiting toxicities were prolonged QTc and thromboembolism .  Thirty-two patients with recurrent glioblastoma multiforme ( GBM ) and 32 patients with recurrent anaplastic gliomas ( AGs ) were treated in the phase II trial , at a dosage of 300 mg/day on 28-day cycles . Six patients ( 4 GBM , 2 AG ) had radiographic response . PFS6 was 6.5 % in the GBM arm and 7.0 % in the AG arm . Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm . Seizures were an unexpected toxicity of therapy . V and etanib did not have significant activity in unselected patients with recurrent malignant glioma PURPOSE This double-blind r and omized phase II trial examined whether v and etanib , an inhibitor of vascular endothelial and epidermal growth factor receptors , could prolong progression-free survival in responding patients with small-cell lung cancer . PATIENTS AND METHODS Eligible patients with complete response ( CR ) or partial response ( PR ) to combination chemotherapy ( + /- thoracic or prophylactic cranial radiation ) received oral v and etanib 300 mg/d or matched placebo .  With 100 patients and 77 events , the study had 80 % power to detect an improvement in median progression-free survival from 4 to 6.5 months ( one-sided , 10%-level test ) . RESULTS Between May 2003 and March 2006 , 107 patients were accrued ; 46 had limited disease and 61 extensive disease . There were fewer patients with a performance status of 0 ( n = 11 v 20 ) , and fewer had CR to initial therapy ( n = 4 v 8) in the v and etanib arm . V and etanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash . Asymptomatic Corrected QT interval ( QTC ) prolongation was observed in eight v and etanib patients . Median progression-free survival for v and etanib and placebo was 2.7 and 2.8 months , respectively ( hazard ratio [ HR ] , 1.01 ; 80 % CI , 0.75 to 1.36 ; one-sided P = .51 ) . Overall survival for v and etanib was 10.6 versus 11.9 months for placebo ( HR , 1.43 ; 80 % CI , 1.00 to 2.05 ; one-sided P = 0.9 ) . In planned subgroup analyses , a significant interaction was noted ( P = .01 ) : limited-stage v and etanib patients had longer overall survival ( HR , 0.45 ; one-sided P = .07 ) and extensive-stage v and etanib patients shorter survival compared with placebo ( HR , 2.27 ; one-sided P = .996 ) . CONCLUSION V and etanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer PURPOSE V and etanib is a once-daily , oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling . The antitumor activity of v and etanib monotherapy or v and etanib with paclitaxel and carboplatin ( VPC ) was compared with paclitaxel and carboplatin ( PC ) in previously untreated patients with non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded , placebo-controlled , r and omized phase II study . Patients were r and omly assigned 2:1:1 to receive v and etanib , VPC , or PC .  Progression-free survival ( PFS ) was the primary end point , and the study was powered to detect a reduced risk of progression with VPC versus PC ( hazard ratio = 0.70 ; one-sided P < .2 ) and to demonstrate noninferiority for v and etanib versus PC . Overall survival was a secondary assessment . RESULTS The risk of progression was reduced for patients receiving VPC ( n = 56 ) versus PC ( n = 52 ; hazard ratio = 0.76 , one-sided P = .098 ) ; median PFS was 24 weeks ( VPC ) and 23 weeks ( PC ) . The v and etanib monotherapy arm ( n = 73 ) was discontinued after a planned interim PFS analysis met the criterion for discontinuation ( hazard ratio > 1.33 v PC ) . Overall survival was not significantly different between patients receiving VPC or PC . Rash , diarrhea , and hypertension were common adverse events ; no pulmonary or CNS hemorrhage events required intervention . CONCLUSION VPC could be safely administered to patients with NSCLC , including those with squamous cell histology and treated brain metastases . Compared with the PC control arm , patients receiving VPC had longer PFS , meeting the prespecified study end point , whereas those receiving v and etanib monotherapy had shorter PFS PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling . This phase III study assessed the efficacy of v and etanib versus erlotinib in unselected patients with advanced non-small-cell lung cancer ( NSCLC ) after treatment failure with one to two prior cytotoxic chemotherapy regimens . PATIENTS AND METHODS One thous and two hundred forty patients were r and omly assigned to receive v and etanib 300 mg/d ( n = 623 ) or erlotinib 150 mg/d ( n = 617 ) . The primary objective was to show superiority in progression-free survival ( PFS ) for v and etanib versus erlotinib . If the difference did not reach statistical significance for superiority , a noninferiority analysis was conducted . RESULTS There was no significant improvement in PFS for patients treated with v and etanib versus erlotinib ( hazard ratio [ HR ] , 0.98 ; 95.22 % CI , 0.87 to 1.10 ; P = .721 ) ; median PFS was 2.6 months for v and etanib and 2.0 months for erlotinib . There was also no significant difference for the secondary end points of overall survival ( HR , 1.01 ; P = .830 ) , objective response rate ( both 12 % ) , and time to deterioration of symptoms for pain ( HR , 0.92 ; P = .289 ) , dyspnea ( HR , 1.07 ; P = .407 ) , and cough ( HR , 0.94 ; P = .455 ) . Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis . Adverse events ( AEs ; any grade ) more frequent with v and etanib than erlotinib included diarrhea ( 50 % v 38 % , respectively ) and hypertension ( 16 % v 2 % , respectively ) ; rash was more frequent with erlotinib than v and etanib ( 38 % v 28 % , respectively ) . The overall incidence of grade ≥ 3 AEs was also higher with v and etanib than erlotinib ( 50 % v 40 % , respectively ) . CONCLUSION In patients with previously treated advanced NSCLC  , v and etanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib . There was a higher incidence of some AEs with v and etanib BACKGROUND & AIMS Inhibitors of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) have shown anti-tumor activities in advanced hepatocellular carcinoma ( HCC ) . The present study evaluated the efficacy and safety of v and etanib , an oral inhibitor of both VEGFR and EGFR , in patients with unresectable advanced HCC . METHODS Eligible patients were r and omized 1:1:1 to receive v and etanib 300mg/day , v and etanib 100mg/day , or placebo .  Upon disease progression , all patients had the option to receive open-label v and etanib 300mg/day . The primary objective was to evaluate tumor stabilization rate ( complete response+partial response+stable disease ⩾4months ) . Secondary assessment s included progression-free survival ( PFS ) , overall survival ( OS ) and safety . Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) . RESULTS Sixty-seven patients were r and omized to v and etanib 300 mg ( n=19 ) , v and etanib 100 mg ( n=25 ) or placebo ( n=23 ) groups . Twenty-nine patients entered open-label treatment .  V and etanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels . In both v and etanib  arms , tumor stabilization rate was not significantly different from placebo : 5.3 % ( v and etanib 300 mg ) , 16.0 % ( v and etanib 100 mg ) and 8.7 % ( placebo ) . DCE-MRI did not detect significant vascular change after v and etanib treatment . Although trends of improved PFS and OS  after v and etanib treatment were found , they were statistically insignificant . The most common adverse events were diarrhea and rash , whose incidence did not differ significantly between treatment groups . CONCLUSIONS V and etanib has limited clinical activity in HCC . The safety profile was consistent with previous studies 
    Output:
    
Our findings demonstrate that the administration of v and etanib leads to a significantly increased risk of diarrhea , which varies in different carcinoma patients .