human
***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: Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuroendocrine tumors ( NETs ) . In recent years , accumulating data has supported their role as antiproliferative agents , capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies , including carcinoid and pancreatic endocrine tumors . A phase III , r and omized , placebo-controlled trial has now demonstrated that octreotide long-acting repeatable ( LAR ) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status , chromogranin A level or age . In addition to significantly lengthening time to tumor progression in the overall study population , subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg , supporting the early use of octreotide LAR in patients with metastatic disease . Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs . Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms .  Specific chemotherapy , interferon‐α ( IFN ) , and somatostatin analogs are established therapies for these patients , but all of them eventually fail . Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients PURPOSE St and ard cytotoxic chemotherapy has limited efficacy in metastatic neuroendocrine tumor patients . Neuroendocrine tumors express vascular endothelial growth factor ( VEGF ) and its receptor ( VEGFR ) . Sunitinib malate , an oral tyrosine kinase inhibitor , has activity against VEGFRs as well as platelet-derived growth factor receptors , stem-cell factor receptor , glial cell line-derived neurotrophic factor , and FMS-like tyrosine kinase-3 . We evaluated the efficacy of sunitinib in a two-cohort , phase II study of advanced carcinoid and pancreatic neuroendocrine tumor patients . PATIENTS AND METHODS Patients were treated with repeated 6-week cycles of oral sunitinib ( 50 mg/d for 4 weeks , followed by 2 weeks off treatment ) . Patients were observed for response , survival , and adverse events . Patient-reported outcomes were assessed . RESULTS Among 109 enrolled patients , 107 received sunitinib ( carcinoid , n = 41 ; pancreatic endocrine tumor , n = 66 ) . Overall objective response rate ( ORR ) in pancreatic endocrine tumor patients was 16.7 % ( 11 of 66 patients ) , and 68 % ( 45 of 66 patients ) had stable disease ( SD ) . Among carcinoid patients , ORR was 2.4 % ( one of 41 patients ) , and 83 % ( 34 of 41 patients ) had SD . Median time to tumor progression was 7.7 months in pancreatic neuroendocrine tumor patients and 10.2 months in carcinoid patients . One-year survival rate was 81.1 % in pancreatic neuroendocrine tumor patients and 83.4 % in carcinoid patients . No significant differences from baseline in patient-reported quality of life or fatigue were observed during treatment . CONCLUSION Sunitinib has antitumor activity in pancreatic neuroendocrine tumors ; its activity against carcinoid tumors could not be definitively determined in this nonr and omized study . R and omized trials of sunitinib in patients with neuroendocrine tumors are warranted 
    Output:
    
agent
***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: Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuroendocrine tumors ( NETs ) . In recent years , accumulating data has supported their role as antiproliferative agents , capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies , including carcinoid and pancreatic endocrine tumors . A phase III , r and omized , placebo-controlled trial has now demonstrated that octreotide long-acting repeatable ( LAR ) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status , chromogranin A level or age . In addition to significantly lengthening time to tumor progression in the overall study population , subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg , supporting the early use of octreotide LAR in patients with metastatic disease . Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs . Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms .  Specific chemotherapy , interferon‐α ( IFN ) , and somatostatin analogs are established therapies for these patients , but all of them eventually fail . Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients PURPOSE St and ard cytotoxic chemotherapy has limited efficacy in metastatic neuroendocrine tumor patients . Neuroendocrine tumors express vascular endothelial growth factor ( VEGF ) and its receptor ( VEGFR ) . Sunitinib malate , an oral tyrosine kinase inhibitor , has activity against VEGFRs as well as platelet-derived growth factor receptors , stem-cell factor receptor , glial cell line-derived neurotrophic factor , and FMS-like tyrosine kinase-3 . We evaluated the efficacy of sunitinib in a two-cohort , phase II study of advanced carcinoid and pancreatic neuroendocrine tumor patients . PATIENTS AND METHODS Patients were treated with repeated 6-week cycles of oral sunitinib ( 50 mg/d for 4 weeks , followed by 2 weeks off treatment ) . Patients were observed for response , survival , and adverse events . Patient-reported outcomes were assessed . RESULTS Among 109 enrolled patients , 107 received sunitinib ( carcinoid , n = 41 ; pancreatic endocrine tumor , n = 66 ) . Overall objective response rate ( ORR ) in pancreatic endocrine tumor patients was 16.7 % ( 11 of 66 patients ) , and 68 % ( 45 of 66 patients ) had stable disease ( SD ) . Among carcinoid patients , ORR was 2.4 % ( one of 41 patients ) , and 83 % ( 34 of 41 patients ) had SD . Median time to tumor progression was 7.7 months in pancreatic neuroendocrine tumor patients and 10.2 months in carcinoid patients . One-year survival rate was 81.1 % in pancreatic neuroendocrine tumor patients and 83.4 % in carcinoid patients . No significant differences from baseline in patient-reported quality of life or fatigue were observed during treatment . CONCLUSION Sunitinib has antitumor activity in pancreatic neuroendocrine tumors ; its activity against carcinoid tumors could not be definitively determined in this nonr and omized study . R and omized trials of sunitinib in patients with neuroendocrine tumors are warranted 
    Output:
    