***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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    Input: We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites , which aim ed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation . Between January 1999 and November 2003 , 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation , excluding well differentiated carcinoid neoplasms , received intravenous ( i.v . ) administration of cisplatinum ( 30 mg m−2 ) and etoposide ( 100 mg m−2 ) on days 1–3 and intramuscular administration of 60 mg lanreotide on day 1 , in a 21-day cycle . All of the patients were evaluable for toxicity and response . The treatment was very well tolerated as no grade 4 toxicity was observed . Four patients achieved a complete response , six a partial response , 12 experienced disease stabilisation and five disease progression . The average time to progression and to survival were 9 and 24 months respectively . These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours Purpose Pasireotide ( SOM230 ) , a novel multireceptor lig and somatostatin analog ( SSA ) , binds with high affinity to four of the five somatostatin receptor subtypes ( sst1–3 , 5 ) . This study evaluated the safety , tolerability , pharmacokinetics , and pharmacodynamics profiles of pasireotide long-acting release ( LAR ) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor ( GEP NET ) refractory to other SSAs . Methods In this r and omized , multicenter , open-label , phase II study , patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were r and omly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20 , 40 , or 60 mg once every 28 days for 3 months . Results Forty-two patients received pasireotide LAR . Adverse events were reported by 34 ( 81 % ) patients , with the most frequently reported including diarrhea , fatigue , abdominal pain , and nausea . Mean fasting glucose levels were increased compared with baseline at all points throughout the study . After the third injection of pasireotide LAR , the median trough plasma concentrations on day 84 were 4.82 , 12.0 , and 19.7 ng/mL in the 20- , 40- , and 60-mg treatment groups , respectively . Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections ( accumulation ratios were approximately 1 from all dose levels ) . Conclusions This study demonstrated that a new , once-monthly , intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET . Steady state levels of plasma pasireotide were achieved after three injections Background Somatostatin analogues ( SSAs ) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours ( NETs ) . This is the first prospect i ve study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs . Methods This was a multicentre , open-label , phase II trial conducted in 17 Spanish specialist centres . Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel  , 120 mg every 28 days over ≤92 weeks . The primary endpoint was progression-free survival ( PFS ) . Secondary endpoints were response rate , tumour biomarkers , symptom control , quality of life ( QoL ) , and safety . Radiographic imaging was assessed by a blinded central radiologist . Results Of 30 patients included in the efficacy and safety analyses , 40 % had midgut tumours and 27 % pancreatic tumours ; 63 % of tumours were functioning . Median PFS time was 12.9 ( 95 % CI : 7.9 , 16.5 ) months , and most patients achieved disease stabilisation ( 89 % ) or partial response ( 4 % ) . No deterioration in QoL was observed . Nineteen patients ( 63 % ) experienced treatment-related adverse events , most frequently diarrhoea and asthenia ; only one treatment-related adverse event ( aerophagia ) was severe . Conclusion Lanreotide Autogel provided effective tumour stabilisation and PFS > 12 months in patients with progressive NETs ineligible for surgery or chemotherapy , with a safety profile consistent with the pharmacology of the class . Trial registration Clinical Trials.gov Identifier NCT00326469 ; EU Clinical Trial Register EudraCT no 2004 - 002871 - 18 PURPOSE Effective systemic therapy for advanced carcinoid is lacking . The combination of bevacizumab ( BEV ) and pegylated ( PEG ) interferon alpha-2b was evaluated among patients with metastatic or unresectable carcinoid tumors . PATIENTS AND METHODS Forty-four patients on stable doses of octreotide  were r and omly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alpha-2b . At disease progression ( PD ) or at the end of 18 weeks ( whichever occurred earlier ) , patients received bevacizumab plus PEG interferon until progression . Functional computer tomography ( CT ) scans were performed to measure effect on tumor blood flow . RESULTS In the bevacizumab arm , four patients ( 18 % ) achieved confirmed partial response ( PR ) , 17 patients ( 77 % ) had stable disease ( SD ) , and one patient ( 5 % ) had PD . In the PEG interferon arm , 15 patients ( 68 % ) had SD and six patients ( 27 % ) had PD . Progression-free survival ( PFS ) rates after 18 weeks of monotherapy were 95 % in bevacizumab versus 68 % on the PEG interferon arm . The overall median PFS for all 44 patients is 63 weeks . Compared with paired baseline measurements on functional CT scans , we observed a 49 % ( P < .01 ) and 28 % ( P < .01 ) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab . No significant changes in tumor blood flow were observed following PEG interferon . PEG interferon alpha-2b treatment was associated with decrease in plasma basic fibroblast growth factor ( bFGF ; P = .04 ) and increase in plasma interleukin-18 ( IL-18 ; P < .01 ) . No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed . CONCLUSION Bevacizumab therapy result ed in objective responses , reduction of tumor blood flow , and longer PFS in patients with carcinoid than PEG interferon treatment We investigated the relationship between the results of the octreotide test and somatostatin receptor ( SSTR ) 2 expression in insulinoma patients , to evaluate the usefulness of this test for predicting SSTR2 expression in insulinomas in Japanese patients . Five females and one male were included in the study . All patients underwent the  octreotide test  before the surgery carried out to resect the tumor , and histopathological examination of the resected tumor was performed by a single experienced pathologist . SSTR2 expression was evaluated by the SSTR2 immunohistochemistry scoring system . Insulinoma was clinical ly diagnosed and surgically resected in all six patients . In the octreotide test , suppression of insulin secretion was sufficient after loading in patients 1 - 4 and 6 . In patient 5 , however , the suppression of insulin secretion was insufficient , which result ed in severe hypoglycemia with endogenous relative hyperinsulinemia after the octreotide loading . The histopathological findings revealed SSTR2 expression in the insulinomas of patients 1 - 4 and 6 , but not in the insulinoma of patient 5 . In conclusion , improvement of hyperinsulinemic hypoglycemia by octreotide in Japanese insulinoma patients was associated with SSTR2 expression in the tumor . Our results suggest that the octreotide test could be useful for predicting SSTR2 expression in the tumor In the CLARINET study , lanreotide Autogel ( depot in USA ) significantly prolonged progression-free survival ( PFS ) in patients with metastatic pancreatic/intestinal neuroendocrine tumours ( NETs ) . We report long-term safety and additional efficacy data from the open-label extension ( OLE ) . Patients with metastatic grade 1/2 ( Ki-67 ≤10 % ) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg ( n=101 ) or placebo ( n=103 ) for 96 weeks or until death/progressive disease ( PD ) in CLARINET study . Patients with stable disease ( SD ) at core study end ( lanreotide/placebo ) or PD ( placebo only ) continued or switched to lanreotide in the OLE . In total , 88 patients ( previously : lanreotide , n=41 ; placebo , n=47 ) participated : 38 % had pancreatic , 39 % midgut and 23 % other/unknown primary tumours . Patients continuing lanreotide reported fewer adverse events ( AEs ) ( all and treatment-related ) during OLE than core study . Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies , except more diarrhoea was considered treatment-related in OLE ( overall diarrhoea unchanged ) . Median lanreotide PFS ( core study r and omisation to PD in core/OLE ; n=101 ) was 32.8 months ( 95 % CI : 30.9 , 68.0 ) . A sensitivity analysis , addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE ( n=13 ) had PD 24 weeks after last core assessment , found median PFS remaining consistent : 30.8 months ( 95 % CI : 30.0 , 31.3 ) . Median time to further PD  after placebo-to-lanreotide switch ( n=32 ) was 14.0 months ( 10.1 ; not reached ) . This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability . CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs OBJECTIVE High-dose somatostatin analogue treatment has shown an antiproliferative effect in one study including patients with neuroendocrine tumours . To explore this therapeutic strategy further , we have studied the effect of a high-dose formula of octreotide , octreotide pamoate , in midgut carcinoid patients . DESIGN AND METHODS Twelve patients with advanced midgut carcinoid tumours with a median duration of disease of more than 5 years were included . All were in a progressive state despite several previous treatment modalities . Octreotide pamoate ( 160 mg ) was given as an intramuscular injection every 2 weeks for 2 months and then monthly . Radiological and biochemical responses were monitored . RESULTS Tumour size and biochemical markers were stabilised for a median of 12 months in 75 % of the patients . Ten patients had symptomatic improvement of flush and diarrhoea . CONCLUSION In this group of patients with advanced midgut carcinoid tumours and progressive disease , octreotide pamoate managed to improve symptoms , and stabilise hormone production and tumour growth in 75 % of the patients . We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours 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 
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Conclusion In this appraisal , we have found some practical aspects that can help to the optimization of somatostatin analog ( SSA ) therapy in patients with well-differentiated GEP-NETs .