***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 The literature on the effect of excess thyroid hormone on ventricular repolarization is controversial . To study whether free thyroxine ( T(4 ) ) and TSH are associated with QTc prolongation we conducted population -based cohort study . This study was conducted as part of the Rotterdam Study and included 365 men and 574 women aged 55 years and older with an electrocardiogram , who were r and omly sample d for the assessment of thyroid status ( free T(4)/TSH ) at baseline , after exclusion of participants with hypothyroidism , use of antithyroid drugs , thyroid hormones or digoxin , left ventricular hypertrophy , and left and right bundle branch block . Endpoints were the length of the QTc interval and risk of borderline QTc prolongation . The associations were examined by means of linear and logistic regression analysis , adjusted for age and gender , diabetes mellitus , myocardial infa rct ion , hypertension , and heart failure . Overall , there was no significant association between TSH and QTc interval ( 0.8 ms ( 95 % confidence interval ( CI ) -3.5 , 5.2 ) in the first quintile compared with the fifth quintile ) . Subjects in the fifth quintile of free T(4 ) did not have an increased QTc interval ( 3.2 ms ( 95 % CI -1.1 , 7.6 ) ) ; stratification on gender showed an increment of 10.9 ms ( 95 % CI 3.4 , 18.3 ) in the fifth quintile in men and 1.1 ms ( 95 % CI -4.2 , 6.3 ) in the fifth quintile of free T(4 ) in women . When compared with subjects in the first quintile , male subjects in the fifth quintile of free T(4 ) had a significantly increased risk of a borderline QTc interval and QTc prolongation ( odds ratio 2.40 ( 95 % CI 1.20 , 4.80 ) ) . High levels of free T(4 ) are associated with substantial QTc prolongation in men of up to 10 ms . The fact that free T(4 ) is also associated with a significantly increased risk of borderline and prolonged QTc values with its risk of sudden cardiac death , endorses the clinical importance of our findings 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 Introduction : V and etanib ( ZACTIMATM ) is a once-daily , oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . V and etanib was evaluated as a monotherapy in a r and omized , double-blind , dose-finding study in Japan . Patients and Methods : Eligible patients with locally advanced or metastatic ( stage IIIB/IV ) or recurrent non-small cell lung cancer , previously treated with chemotherapy , were r and omized to receive once-daily oral v and etanib 100 , 200 , or 300 mg ( 1:1:1 ) . The primary objective was to determine the objective response rate for each v and etanib dose . Results : Fifty-three patients received v and etanib ( 100 mg , n = 17 ; 200 mg , n = 18 ; 300 mg , n = 18 ) . The objective response rate in each dose arm was 17.6 % ( 3 of 17 ; 100 mg ) , 5.6 % ( 1 of 18 ; 200 mg ) , and 16.7 % ( 3 of 18 ; 300 mg ) . Common adverse events included rash , diarrhea , hypertension , and asymptomatic QTc prolongation . The adverse event profile was generally consistent with that reported previously for agents that inhibit the VEGFR or EGFR signaling pathways . Among the three responders evaluated for EGFR mutation , two had no mutation , and in one case , the EGFR mutation status could not be determined by direct DNA sequencing and amplification refractory mutation system assay of EGFR exons 19–21 . Baseline plasma VEGF levels appeared to be lower in patients who experienced clinical benefit after v and etanib treatment . Conclusion : In Japanese patients with advanced non-small cell lung cancer , v and etanib monotherapy ( 100–300 mg/d ) demonstrated antitumor activity with an acceptable safety and tolerability profile 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 V and etanib ( ZACTIMA ) is a once-daily oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor , epidermal growth factor receptor , and rearranged during transfection signaling . This r and omized ( 1:1 ) , double-blind study evaluated v and etanib ( 100 mg/day ) or placebo in combination with docetaxel ( D ; 75 mg/m(2 ) every 3 weeks ) and prednisolone ( P ; 2 x 5 mg/day ) in 86 patients with metastatic hormone-refractory prostate cancer ( mHRPC ) . The primary assessment was prostate-specific antigen ( PSA ) response ( confirmed reduction of > or=50 % from baseline ) and a greater number of patients showed a PSA response with placebo + DP ( 67 % ) versus v and etanib + DP ( 40 % ) ; hazard ratio = 2.23 ( one-sided 80 % confidence limit = 2.90 ; one-sided p = 0.99 ) . More patients experienced progression events ( disease progression or death from any cause ) with v and etanib + DP ( 65 % ) versus placebo + DP ( 60 % ) ; hazard ratio = 1.13 ( one-sided 80 % confidence limit = 1.44 ; one-sided p = 0.67 ) . The overall incidence of adverse events was similar in both groups , although more patients experienced adverse events , leading to permanent discontinuation with v and etanib + DP ( 28 % ) versus placebo + DP ( 12 % ) . However , the safety and tolerability profile for v and etanib was similar to that previously reported ; adverse events that occurred more frequently in the v and etanib + DP arm were hypertension ( 14 % vs. 2 % ) , erythematous rash ( 14 % vs. 2 % ) , and exfoliative rash ( 12 % vs. 2 % ) . In this study of patients with mHRPC , v and etanib + DP did not demonstrate any efficacy benefit , compared with placebo + DP BACKGROUND V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) , epidermal growth factor receptor ( EGFR ) , and rearranged during transfection ( RET ) tyrosine kinases . In a r and omised phase 2 study in patients with previously treated non-small-cell lung cancer ( NSCLC ) , adding v and etanib 100 mg to docetaxel significantly improved progression-free survival ( PFS ) compared with docetaxel alone , including a longer PFS in women . These results supported investigation of the combination in this larger , definitive phase 3 trial ( ZODIAC ) . METHODS Between May , 2006 , and April , 2008 , patients with locally advanced or metast 
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/ SIGNIFICANCE Treatment with v and etanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation .
Different cancer types and treatment duration s may affect the risk of developing high- grade QTc interval prolongation