Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors Activity of sunitinib in patients with advanced neuroendocrine tumors.
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
BACKGROUND Neuroendocrine tumours ( NET ) most commonly metastasize to the liver .
Hepatic resection of NET hepatic metastases ( NETHM ) has been shown to improve symptomology and survival .
METHODS A systematic review of clinical studies before September 2010 was performed to examine the efficacy of hepatic resection for NETHM .