***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 This trial evaluated the efficacy and safety of sorafenib plus gemcitabine/cisplatin in chemotherapy-naive patients with unresectable stage IIIB to IV nonsquamous non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between February 2007 and March 2009 , 904 patients were r and omly assigned to daily sorafenib ( 400 mg twice a day ) or matching placebo plus gemcitabine ( 1,250 mg/m(2 ) per day on days 1 and 8) and cisplatin ( 75 mg/m(2 ) on day 1 ) for up to six 21-day cycles . Because of safety findings from the Evaluation of Sorafenib , Carboplatin and Paclitaxel Efficacy in NSCLC ( ESCAPE ) trial , patients with squamous cell histology were withdrawn from the trial in February 2008 and excluded from analysis . The primary end point was overall survival ( OS ) , and secondary end points included progression-free survival ( PFS ) and time-to-progression ( TTP ) . RESULTS The primary analysis population consisted of 772 patients ( sorafenib , 385 ; placebo , 387 ) ; the two groups had similar demographic and baseline characteristics . Median OS was similar in the sorafenib and placebo groups ( 12.4 v 12.5 months ; hazard ratio [ HR ] , 0.98 ; P = .401 ) . By investigator assessment , sorafenib improved median PFS ( 6.0 v 5.5 months ; HR , 0.83 ; P = .008 ) and TTP ( 6.1 v 5.5 months ; HR , 0.73 ; P < .001 ) . Grade 3 to 4 drug-related adverse events more than two-fold higher in the sorafenib group included h and -foot skin reaction ( 8.6 % v 0.3 % ) , fatigue ( 7.3 % v 3.6 % ) , rash ( 5.7 % v 0.5 % ) , and hypertension ( 4.2 % v 1.8 % ) . No unexpected toxicities were observed . CONCLUSION This study did not meet its primary end point of improved OS when sorafenib was added to first-line gemcitabine/cisplatin in patients with advanced nonsquamous NSCLC . Identification of predictive biomarkers is warranted in future trials of sorafenib Purpose : Hypertension is a commonly reported side effect in antiangiogenic therapy . We investigated the hypothesis that telatinib , a small molecule angiogenesis inhibitor , impairs vascular function , induces rarefaction , and causes hypertension . Experimental Design : A side- study was done in a phase I trial of telatinib , a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3 , platelet-derived growth factor receptor , and c-KIT in patients with advanced solid tumors . Measurements of blood pressure , flow-mediated dilation , nitroglycerin-mediated dilation , aortic pulse wave velocity , skin blood flux with laser Doppler flow , and capillary density with sidestream dark field imaging were done at baseline and after 5 weeks of treatment . Blood pressure and proteinuria were measured weekly . Results : Mean systolic and diastolic blood pressure values increased significantly at + 6.6 mm Hg ( P = 0.009 ) and + 4.7 mm Hg ( P = 0.016 ) , respectively . Mean flow-mediated dilation and mean nitroglycerin-mediated dilation values significantly decreased by −2.1 % ( P = 0.003 ) and −5.1 % ( P = 0.001 ) , respectively . After 5 weeks of treatment , mean pulse wave velocity significantly increased by 1.2 m/s ( P = 0.001 ) . A statistically significant reduction of mean skin blood flux of 532.8 % arbitrary units was seen ( P = 0.015 ) . Capillary density statistically significantly decreased from 20.8 to 16.7 capillary loops ( P = 0.015 ) . Proteinuria developed or increased in six patients during telatinib treatment . Conclusion : The increase in blood pressure observed in the treatment with telatinib , an angiogenesis inhibitor , may be caused by functional or structural rarefaction BACKGROUND Hypertension ( HTN ) , a recognized adverse effect of angiogenesis inhibitors , may be a potential biomarker of activity of these agents . We conducted a retrospective analysis to examine the incidence and predictors of the development of on-treatment HTN with the vascular endothelial growth factor receptor tyrosine kinase inhibitor cediranib , and the relationship of this adverse event with treatment outcomes . PATIENTS AND METHODS BR24 was a double-blind placebo-controlled  phase II trial of carboplatin/paclitaxel chemotherapy with either daily oral cediranib or placebo  in patients ( n = 296 ) with advanced non-small-cell lung cancer ( NSCLC ) . Exploratory analyses characterized relationships between HTN , baseline variables , and efficacy outcomes . RESULTS New onset or worsening of preexisting HTN ( treatment-emergent HTN ) was more frequent in patients receiving cediranib ( 68 versus 45 % , P < 0.0001 ) . Factors associated with HTN in all r and omized patients were good performance status and treatment with cediranib . In both arms , treatment-emergent HTN was associated with improved efficacy outcomes , but there was no evidence of a differential treatment effect , with nonsignificant interaction P values . CONCLUSIONS In advanced NSCLC , HTN is frequent in patients receiving chemotherapy  , with or without cediranib . The development of HTN was favorably prognostic in these patients , but not predictive of a differential outcome with cediranib Background : Anlotinib ( AL3818 ) is a novel multitarget tyrosine kinase inhibitor , inhibiting tumour angiogenesis and proliferative signalling . The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer ( RA-NSCLC ) . Methods : Eligible patients were r and omised 1 : 1 to receive anlotinib ( 12 mg per day , per os ; days 1–14 ; 21 days per cycle ) or a placebo . The primary end point was progression-free survival ( PFS ) . Results : A total of 117 eligible patients enrolled from 13 clinical centres in China were analysed in the full analysis set . No patients received immune check-point inhibitors and epidermal growth factor receptor status was unknown in 60.7 % of the population . PFS was better with anlotinib compared with the placebo ( 4.8 vs 1.2 months ; hazard ratio (HR)=0.32 ; 95 % confidence interval ( CI ) , 0.20–0.51 ; P<0.0001 ) , as well as overall response rate ( ORR ) ( 10.0 % ; 95 % CI , 2.4–17.6 % vs 0 % ; 95 % CI , 0–6.27 % ; P=0.028 ) . The median overall survival ( OS ) was 9.3 months ( 95 % CI , 6.8–15.1 ) for the anlotinib group and 6.3 months ( 95 % CI , 4.3–10.5 ) for the placebo group ( HR=0.78 ; 95 % CI , 0.51–1.18 ; P=0.2316 ) . Adverse events were more frequent in the anlotinib than the placebo group . The percentage of grade 3–4 treatment-related adverse events was 21.67 % in the anlotinib group . Conclusions : Anlotinib as a third-line treatment provided significant PFS benefits to patients with RA-NSCLC when compared with the placebo , and the toxicity profiles showed good tolerance PURPOSE This phase II/III double-blind study assessed efficacy and safety of cediranib with st and ard chemotherapy as initial therapy for advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( area under the serum concentration-time curve 6 ) were given every 3 weeks , with daily oral cediranib or placebo at 30 mg ( first 45 patients received 45 mg ) . Progression-free survival ( PFS ) was the primary outcome of the phase II interim analysis ; phase III would proceed if the hazard ratio ( HR ) for PFS < or = 0.77 and toxicity were acceptable . Results A total of 296 patients were enrolled , 251 to the 30-mg cohort . The phase II interim analysis demonstrated a significantly higher response rate ( RR ) for cediranib than for placebo , HR of 0.77 for PFS , no excess hemoptysis , and a similar number of deaths in each arm . The study was halted to review imbalances in assigned causes of death . In the primary phase II analysis ( 30-mg cohort ) , the adjusted HR for PFS was 0.77 ( 95 % CI , 0.56 to 1.08 ) with a higher RR for cediranib than for placebo ( 38 % v 16 % ; P < .0001 ) . Cediranib patients had more hypertension , hypothyroidism , h and -foot syndrome , and GI toxicity . Hypoalbuminemia , age > or = 65 years , and female sex predicted increased toxicity . Survival up date ( N = 296 ) 10 months after study unblinding favored cediranib over placebo ( median of 10.5 months v 10.1 months ; HR , 0.78 ; 95 % CI , 0.57 to 1.06 ; P = .11 ) . Causes of death in the cediranib 30-mg cohort were NSCLC ( 81 % ) , protocol toxicity + /- NSCLC ( 13 % ) , and other ( 6 % ) ; for the placebo group , they were 98 % , 0 % , and 2 % , respectively . CONCLUSION The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS , but does not appear tolerable at a 30-mg dose . Consequently , the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a r and omized , double-blind , placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC Using MRI techniques , we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset , is prolonged but reversible , and has the significant clinical benefit of alleviating edema . Reversal of normalization began by 28 days , though some features persisted for as long as four months . Basic FGF , SDF1alpha , and viable circulating endothelial cells ( CECs ) increased when tumors escaped treatment , and circulating progenitor cells ( CPCs ) increased when tumors progressed after drug interruption . Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor BACKGROUND V and etanib ( ZACTIMA ; ZD6474 ) is a once-daily , oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling . The safety and tolerability of v and etanib plus pemetrexed was assessed in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with previously treated NSCLC ( stage IIIB/IV ) received once-daily oral v and etanib ( 100 or 300 mg ) with pemetrexed ( 500 mg/m(2 ) i.v . infusion every 21 days ) . RESULTS Patients received v and etanib 100 mg + pemetrexed ( n=10 ) or v and etanib 300 mg + pemetrexed ( n=11 ) . The protocol definition of a tolerable dose [ v and etanib-related dose-limiting toxicity ( DLT ) in less than 2 patients ] was met in both dose cohorts , with one DLT reported in each : asymptomatic QTc prolongation ( > 100 ms increase from baseline , but absolute QTc<500 ms ) in the 100 mg cohort and interstitial lung disease , which resolved after steroid therapy , in the 300 mg cohort . The most common adverse events were rash , anorexia , fatigue and diarrhea ( all n=10 ) . CONCLUSION V and etanib and pemetrexed in combination were generally well tolerated in patients with advanced NSCLC Background The efficacy and safety of axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non – small-cell lung cancer ( NSCLC ) . Methods Overall , 170 patients were r and omly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 50 
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The incidence of some high grade ( ≥ 3 ) AEs increased , such as hemorrhage , hypertension and neutropenia .
Conclusions : Our study demonstrated that regimens with VEGFR-TKIs combined with chemotherapy  improved PFS , ORR and DCR in patients with advanced NSCLC , but had no impact on OS .
VEGFR-TKIs induced more frequent and serious AEs compared with control therapies