***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: Telotristat ethyl , a tryptophan hydroxylase inhibitor , was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome ( CS ) experiencing ≥4 bowel movements per day ( BMs/day ) while on somatostatin analogs ( SSAs ) .  TELECAST , a phase 3 companion study , assessed the safety and efficacy of telotristat ethyl in patients with CS ( diarrhea , flushing , abdominal pain , nausea or elevated urinary 5-hydroxyindoleacetic acid ( u5-HIAA ) ) with < 4 BMs/day on SSAs ( or ≥1 symptom or ≥4 BMs/day if not on SSAs ) during a 12-week double-blind treatment period followed by a 36-week open-label extension ( OLE ) . The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events ( TEAEs ) and percent change from baseline in 24-h u5-HIAA at week 12 . Patients ( N = 76 ) were r and omly assigned ( 1:1:1 ) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day ( tid ) ; 67 continued receiving telotristat ethyl 500 mg tid during the OLE . Through week 12 , TEAEs were generally mild to moderate in severity ; 5 ( placebo ) , 1 ( telotristat ethyl 250 mg ) and 3 ( telotristat ethyl 500 mg ) patients experienced serious events , and the rate of TEAEs in the OLE was comparable . At week 12 , significant reductions in u5-HIAA from baseline were observed , with Hodges – Lehmann estimators of median treatment differences from placebo of −54.0 % ( 95 % confidence limits , −85.0 % , −25.1 % , P < 0.001 ) and −89.7 % ( 95 % confidence limits , −113.1 % , −63.9 % , P < 0.001 ) for telotristat ethyl 250 mg and 500 mg . These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea ( Clinical Trials.gov identifier : Nbib2063659 ) BACKGROUND : Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome . The octapeptide lanreotide is available in slow release form , which could eliminate the necessity of twice a day injections as with octreotide . PATIENTS AND METHODS : 39 patients with carcinoid syndrome were included in a prospect i ve multicentre study . Patients received lanreotide 30 mg intramuscularly every 14 days for six months . The number and intensity of flushing episodes and bowel movements , urinary 5 hydroxy-indolacetic acid ( 5 HIAA ) concentrations , and variations of tumour mass were recorded . RESULTS : After one month of treatment , flushing episodes ( median ( range ) ) decreased significantly ( 3 ( 0.3 - 24 ) episodes per day v 1 ( 0 - 15 ) , p = 0.04 ) and completely resolved in 39 % of the patients . A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea . Urinary 5 HIAA concentrations were unchanged in 57 % of the patients and decreased in 18 % . After six months of treatment , the actuarial proportions of patients with at least a 50 % decrease in the number of flushing episodes and bowel movements were 54 % and 56 % , respectively . Forty two per cent of the patients who were treated for six months had at least a 50 % reduction in 5 HIAA values . No clear signs of regression of tumours were seen in any of the patients . Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25 % of the patients . Biliary lithiasis appeared in two patients after six months of lanreotide . CONCLUSION : Lanreotide , 30 mg intramuscularly every other week , is an effective and convenient treatment in patients with the carcinoid syndrome The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy ( PRRT ) and in defining the minimum requirements for PRRT . It is not these guidelines ' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used , and their availability is governed by varying international regulations . However , a recent r and omized controlled trial , NETTER-1 , has provided evidence that may establish 177Lu-DOTA-octreotate ( LutaThera ® ) as the first widely approved agent . It also makes recommendations on what minimal patient , tumour , and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of 302 patients were enrolled , of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo . Median progression-free survival was 11·0 months ( 95 % CI 9·2 - 13·3 ) in the everolimus group and 3·9 months ( 3·6 - 7·4 ) in the placebo group . Everolimus was associated with a 52 % reduction in the estimated risk of progression or death ( hazard ratio [ HR ] 0·48 [ 95 % CI 0·35 - 0·67 ] , p<0·00001 ) . Although not statistically significant , the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death ( HR 0·64 [ 95 % CI 0·40 - 1·05 ] , one-sided p=0·037 , whereas the boundary for statistical significance was 0·0002 ) . Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis ( in 18 [ 9 % ] of 202 patients in the everolimus group vs 0 of 98 in the placebo group ) , diarrhoea ( 15 [ 7 % ] vs 2 [ 2 % ] ) , infections ( 14 [ 7 % ] vs 0 ) , anaemia ( 8 [ 4 % ] vs 1 [ 1 % ] ) , fatigue ( 7 [ 3 % ] vs 1 [ 1 % ] ) , and hyperglycaemia ( 7 [ 3 % ] vs 0 ) . INTERPRETATION Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours . The safety findings were consistent with the known side-effect profile of everolimus . Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours , including those arising from the pancreas , lung , and gastrointestinal tract . FUNDING Novartis Pharmaceuticals Corporation Purpose Preliminary studies suggested that telotristat ethyl , a tryptophan hydroxylase inhibitor , reduces bowel movement ( BM ) frequency in patients with carcinoid syndrome . This placebo-controlled phase III study evaluated telotristat ethyl in this setting . Patients and Methods Patients ( N = 135 ) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy  received ( 1:1:1 ) placebo , telotristat ethyl 250 mg , or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period . The primary end point was change from baseline in BM frequency . In an open-label extension , 115 patients subsequently received telotristat ethyl 500 mg . Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg ( P < .001 ) and ‒0.69 for telotristat ethyl 500 mg ( P < .001 ) . At week 12 , mean BM frequency reductions per day for placebo , telotristat ethyl 250 mg , and telotristat ethyl 500 mg were -0.9 , -1.7 , and -2.1 , respectively . Responses , predefined as a BM frequency reduction ≥ 30 % from baseline for ≥ 50 % of the double-blind treatment period , were observed in 20 % , 44 % , and 42 % of patients given placebo , telotristat ethyl 250 mg , and telotristat ethyl 500 mg , respectively . Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P < .001 ) . Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl . Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment . Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs , treatment with telotristat ethyl was generally safe and well tolerated and result ed in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid CONTEXT Carcinoid syndrome ( CS ) is associated with elevated serotonin , diarrhea , flushing , and increased risk of valvular heart disease . Many patients respond to somatostatin analogs initially , but response diminishes in most patients . Additional options are needed . OBJECTIVE To assess whether telotristat etiprate ( TE ) can reduce gastrointestinal symptoms in CS and reduce urinary 5-hydroxyindoleacetic acid ( u5-HIAA ; a biomarker of serotonin ) . DESIGN A prospect i ve , exploratory , dose-escalating 12-week , open-label , multicenter study of TE with efficacy and safety analyses . SETTING A multicenter study . PATIENTS Eligible patients had metastatic , well-differentiated , neuroendocrine tumors and CS with ≥ four bowel movements ( BMs ) per day .  Somatostatin analog use was allowed . INTERVENTIONS TE , a novel oral inhibitor of peripheral serotonin synthesis . MAIN OUTCOME MEASURES Primary : safety . Secondary : daily BMs , stool form , and u5-HIAA . RESULTS Fifteen patients were enrolled , and 14 completed the treatment period . All patients experienced reductions in BMs per day ( mean decrease , 43.5 % ) . A 74.2 % mean reduction in u5-HIAA , the main metabolite of serotonin , was observed , with generally greater reductions in patients with greater reductions in BMs per day . Nine patients ( 75 % ) reported " adequate relief " of gastrointestinal symptoms at 12 weeks , compared with two ( 17 % ) at baseline . Stool form and flushing also improved . Adverse events were mostly gastrointestinal ( n = 10 ; 67 % ) , consistent with underlying illness ; three adverse events were serious ( abdominal pain , diarrhea , and gastroenteritis ) but were judged unrelated . CONCLUSION TE was generally safe and well tolerated . Patients experienced substantial improvement in CS and reductions in u5-HIAA , consistent with the mechanism of action of TE . These results support further evaluation in phase 3 studies 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 
    Output:
    
Somatostatin analogues provided substantial symptom relief for patients with carcinoid syndrome .
For refractory symptoms , an increased dose of somatostatin analogue or addition of telotristat ethyl were valuable options .
Interventions were generally well tolerated , with few serious treatment-related adverse events .