***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with  placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline )  were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel  included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company Summary Background Cisplatin and fluoropyrimidine ( CF ) are st and ard first- line treatment in advanced gastric cancer , but no second-line treatment has yet been established . We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib ( S ) , and Oxaliplatin as second-line therapy . Methods Patients with progressive gastric adenocarcinoma after CF- first-line , ECOG 0–2 , and measurable disease were included . The primary objective was PFS . Treatment doses were Oxaliplatin 130 mg/m2/3 weeks and Sorafenib 800 mg/bid/d . Results We included 40 patients . CR was 2.5 % and SD was 47.2 % . Grade 3–4 toxic effects were neutropenia ( 9.8 % ) , thrombocytopenia ( 7.3 % ) , neurotoxicity ( 4.9 % ) and diarrhea ( 4.9 % ) . Median PFS was 3 months ( 95 % CI : 2.3–4.1 ) and median OS was 6.5 months ( 95 % CI : 5.2–9.6 ) . Time to progression ( TTP ) to first line therapy was a prognosis factor . Median OS was 9.7 months when time-to-progression during first-line chemotherapy was > 6 months and 5.6 m when it was < 6 months ( p = 0.04 ) . Conclusions Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis . The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe , but our results do not support the implementation of a phase III trial Summary Purpose . This phase II , open-label , multicenter study assessed the oral , multitargeted , tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy . Experimental design . Patients received sunitinib 50 mg/day on Schedule 4/2 ( 4 weeks on treatment , followed by 2 weeks off treatment ) . The primary endpoint was objective response rate ; secondary endpoints included clinical benefit rate , duration of response , progression-free survival ( PFS ) , overall survival ( OS ) , pharmacokinetics , pharmacodynamics , safety and tolerability , and quality of life . Results . Of 78 patients enrolled , most had gastric adenocarcinoma ( 93.6 % ) and metastatic disease ( 93.6 % ) . All were evaluable for safety and efficacy . Two patients ( 2.6 % ) had partial responses and 25 patients ( 32.1 % ) had a best response of stable disease for ≥6 weeks . Median PFS was 2.3 months ( 95 % confidence interval [ CI ] , 1.6–2.6 months ) and median OS was 6.8 months ( 95 % CI , 4.4–9.6 months ) . Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6 % and 29.4 % of patients , respectively , and the most common non-hematologic adverse events were fatigue , anorexia , nausea , diarrhea , and stomatitis . Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports . There were no marked associations between baseline soluble protein levels , or changes from baseline , and measures of clinical outcome . Conclusions . The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer , its role in combination with chemotherapy merits further study Background : This study aim ed to determine whether combination S-1 plus cisplatin ( CDDP ) therapy , the most widely used therapy for Japanese patients with advanced gastric cancer , and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment . Methods : Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were r and omised into two groups : TSU-68 plus S-1/CDDP ( group A ) and S-1/CDDP ( group B ) groups . Both patient groups received identical S-1 and CDDP dosages . TSU-68 was orally administered for 35 consecutive days . Group B patients received S-1 orally twice daily for three consecutive weeks , followed by intravenous CDDP on day 8 . The primary endpoint was progression-free survival ( PFS ) . Results : Median PFS periods were 208 and 213 days in groups A and B , respectively ( P=0.427 ) . Median survival periods for groups A and B were 497.0 and 463.5 days , respectively ( P=0.219 ) . No statistically significant differences were noted for PFS , survival or the adverse event ( AE ) incidence rate . All AEs were expected according to previous reports for TSU-68 , TS-1 , and CDDP . Conclusion : Combination therapy involving TSU-68 , S-1 , and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers . However , factors related to therapeutic efficacy should be investigated further BACKGROUND Peri-operative chemotherapy and surgery is a st and ard treatment of localised oesophagogastric adenocarcinoma ; however , the outcomes remain poor . PATIENTS AND METHODS ST03 is a multicentre , r and omised , phase II/III study comparing peri-operative ECX with or without bevacizumab ( ECX-B ) . The primary outcome measure of phase II ( n = 200 ) was safety , specifically gastrointestinal ( GI ) perforation rates and cardiotoxicity . RESULTS Two hundred patients were r and omised between October 2007 and April 2010 . Ninety-one/101 ( 90 % ) ECX and 86/99 ( 87 % ) ECX-B patients completed pre-operative chemotherapy ; 7 ECX and 9 ECX-B patients stopped due to toxicity . Gastrointestinal perforations ( 3 ECX , 1 ECX-B ) , cardiac events ( 1 ECX , 4 ECX-B ) and venous thromboembolic events ( VTEs , 8 ECX , 7 ECX-B ) were uncommon . Arterial thromboembolic events ( ATEs , myocardial infa rct ion ( MI ) or cerebrovascular accident ) were more frequent with ECX-B ( 5 versus 1 with ECX ) . Delayed wound healing , anastomotic leaks and GI bleeding rates were similar . More asymptomatic left ventricular ejection fraction ( LVEF ) falls ( ≥15 % and /or to < 50 % ) occurred with ECX-B ( 21.2 % versus 11.1 % with ECX ) . Clinical ly significant falls ( ≥10 % to below lower limit of normal , LLN ) occurred in ( 15.3 % ) and ( 8.9 % ) respectively , with no associated cardiac failure ( median 22 months follow-up ) . CONCLUSIONS Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes We design ed a single-arm , open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx ( capecitabine and oxaliplatin ) in metastatic /recurrent advanced gastric cancer ( AGC ) patients . Previously untreated AGC patients received capecitabine ( 850 mg/m2 bid , day 1–14 ) plus oxaliplatin ( 130 mg/m2 , day 1 ) in combination with pazopanib ( 800 mg , day 1–21 ) every three weeks . Treatment was continued until progression of the disease or intolerable toxicity was observed . In all , 66 patients were treated with pazopanib plus CapeOx .  The median age of the patients was 51.5 years ( range , 23.0–77 ) , and the median ECOG performance status was 1 ( 0–1 ) . Among all 66 patients , one complete response and 37 partial responses were observed ( overall response rate , 62.4 % ; 95 % confidence interval ( CI ) , 45.7–73.5 % accounting for the 2-stage design of this trial ) . Stable disease was observed in 23 patients ( 34.8 % ) , revealing a 92.4 % disease control rate . The median progression free survival and overall survival were 6.5 months ( 95 % CI , 5.6–7.4 ) and 10.5 months ( 95 % CI , 8.1–12.9 ) , respectively . Thirty-four patients ( 51.5 % ) experienced a treatment-related toxicity of grade 3 or more . The most common toxicities of grade 3 or more were neutropenia ( 15.1 % ) , anemia ( 10.6 % ) , thrombocytopenia ( 10.6 % ) , anorexia ( 7.6 % ) , nausea ( 3.0 % ) , and vomiting ( 3.0 % ) . There were no treatment-related deaths . The combination of pazopanib and CapeOx showed moderate activity and an acceptable toxicity profile as a first-line treatment in metastatic / recurrent AGC patients ( Clinical Trials.gov NCT01130805 ) PURPOSE We evaluated the activity of regorafenib , an oral multikinase inhibitor , in advanced gastric adenocarcinoma . PATIENTS AND METHODS We conducted an international ( Australia and New Zeal and , South Korea , and Canada ) r and omized phase II trial in which patients were r and omly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease ( one v two ) and region . Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 
    Output:
    
Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer .
Overall , agents that specifically target the vascular endothelial growth factor lig and or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors