***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: To evaluate the treatment of advanced islet-cell carcinoma , we r and omly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil . Each regimen was given in five-day courses . The most frequent toxic effects were nausea and vomiting , mild and reversible renal toxicity , and bone-marrow depression with the combination regimen . The combination had advantages over streptozocin alone in overall rate of response ( 63 vs. 36 per cent ) and in rates of complete response ( 33 vs. 12 per cent ) . There was no evidence of a preferential response among types of functional tumors . Objective responses were generally of long duration ( median , 17 months ) and of substantive clinical benefit . Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone ( medians , 26 and 16 1/2 months ) , but this difference is not statistically significant . In spite of gastrointestinal side effects , streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma The aim of this r and omized multicenter phase III trial was to compare chemotherapy and interferon ( IFN ) in patients with metastatic carcinoid tumors . Patients with documented progressive , unresectable , metastatic carcinoid tumors were r and omized between 5-fluorouracil plus streptozotocin ( day 1 - 5 ) and recombinant IFN-alpha-2a ( 3 MU x 3 per week ) . Primary endpoint was progression-free survival ( PFS ) . From February 1998 to June 2004 , 64 patients were included . The two arms were well matched for median age , sex ratio , PS 0 - 1 , previous chemotherapy , surgery , or radiotherapy . The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN ( hazard ratio=0.75 ( 0.41 - 1.36 ) ) . Overall survival ( OS ) , tolerance , and effects on carcinoid symptoms were not significantly different . Despite a trend in favor of IFN , there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild PURPOSE Optimal treatments for metastatic carcinoid tumor remain undefined , and the role of chemotherapy for symptomatic patients with progressive disease is uncertain . PATIENTS AND METHODS Two hundred forty-nine patients with advanced carcinoid tumors were r and omized to either doxorubicin with fluorouracil ( FU/DOX ) or streptozocin with fluorouracil ( FU/STZ ) . Patients crossed over to the dacarbazine ( DTIC ) treatment after disease progression following first-line treatment ( either FU/DOX or FU/STZ ) , and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function . RESULTS In the r and omized group , there was no difference between FU/DOX and FU/STZ in response rates ( 15.9 % v 16 % ) and progression-free survival ( 4.5 v 5.3 months ) . FU/STZ ( 24.3 months ) was superior to FU/DOX ( 15.7 months ; P = .0267 ) in median survival . The response rate of crossover DTIC treatment was 8.2 % , with a median survival of 11.9 months . Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ , and mild to moderate renal toxicity was reported in 40 ( 34.8 % ) of 115 patients in the FU/STZ arm . CONCLUSION Response to all three treatment regimens were modest . FU/STZ improved survival compared with the doxorubicin-based regimen , suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors These guidelines up date previous guidance published in 2005 . They have been revised by a group who are members of the UK and Irel and Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology , the Society for Endocrinology , the Association of Surgeons of Great Britain and Irel and ( and its Surgical Specialty Associations ) , the British Society of Gastrointestinal and Abdominal Radiology and others . The authors hip represents leaders of the various groups in the UK and Irel and Neuroendocrine Tumour Society , but a large amount of work has been carried out by other specialists , many of whom attended a guidelines conference in May 2009 . We have attempted to represent this work in the acknowledgements section . Over the past few years , there have been advances in the management of neuroendocrine tumours , which have included clearer characterisation , more specific and therapeutically relevant diagnosis , and improved treatments . However , there remain few r and omised trials in the field and the disease is uncommon , hence all evidence must be considered weak in comparison with other more common cancers . BACKGROUND The combination of streptozocin and fluorouracil has become the st and ard therapy for advanced islet-cell carcinoma . However , doxorubicin has also been shown to be active against this type of tumor , as has chlorozotocin , a drug that is structurally similar to streptozocin but less frequently causes vomiting . METHODS In this multicenter trial , we r and omly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens : streptozocin plus fluorouracil , streptozocin plus doxorubicin , or chlorozotocin alone .  The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens . RESULTS Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression , measured objective ly ( 69 percent vs. 45 percent , P = 0.05 ) , and the length of time to tumor progression ( median , 20 vs. 6.9 months ; P = 0.001 ) . Streptozocin plus doxorubicin also had a significant advantage in terms of survival ( median , 2.2 vs. 1.4 years ; P = 0.004 ) that was accentuated when we considered long-term survival ( greater than 2 years ) . Chlorozotocin alone produced a 30 percent regression rate , with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil . Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent , and the responses were transient . Toxic reactions to all regimens included vomiting , which was least severe with chlorozotocin ; hematologic depression ; and , with long-term therapy , renal insufficiency . CONCLUSIONS The combination of streptozocin and doxorubicin is superior to the current st and ard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma . Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil , but it produces fewer gastrointestinal side effects than the regimens containing streptozocin . It therefore merits study as a constituent of combination drug regimens 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 BACKGROUND Cytotoxic chemotherapy is widely used for advanced , unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours ( NETs ) and the most commonly used regimen combines 5-fluorouracil with streptozocin . The NET01 trial was design ed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin . METHODS Patients with advanced , unresectable NETs of pancreatic , gastrointestinal foregut or unknown primary site were r and omised to receive three-weekly capecitabine ( Cap ) 625 mg/m(2 ) twice daily orally , streptozocin ( Strep ) 1.0 g/m(2 ) intravenously on day 1 , with or without cisplatin ( Cis ) 70 mg/m(2 ) intravenously on day 1 . The primary outcome measure was objective response . Secondary outcome measures included progression-free and overall survival , quality of life , toxicity and biochemical response . RESULTS 86 ( 44 CapStrep , 42 CapStrepCis ) patients were r and omised . Best objective response rate was 12 % ( 95 % confidence interval (CI)=2 - 22 % ) with CapStrep and 16 % ( 95 % CI=4 - 27.4 % ) with CapStrepCis . Disease-control rate was 80 % with CapStrep and 74 % with CapStrepCis . The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis . 44 % of CapStrep and 68 % of CapStrepCis patients experienced grade ≥3 adverse events . INTERPRETATION The efficacies of the novel CapStrep±Cis regimens were very similar . CapStrep was better tolerated than CapStrepCis . The trial was registered as EudraCT : 2004 - 005202 - 71 and IS RCT N : 35124268 In a r and omized controlled study , 20 patients with malignant carcinoid tumors were included . Ten patients received streptozocin plus 5-fluorouracil for 6 months and another 10 human leukocyte interferon ( IFN ) . After 6 months of treatment , an objective tumor response was noted in five of the patients treated with IFN ( 50 % ) but in none of the patients on chemotherapy .  Stable disease was found in five patients ( 50 % ) on IFN treatment and four ( 40 % ) on chem 
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Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors .
There is currently no evidence that one chemotherapeutic regimen is significantly better than the other , nor is interferon better than chemotherapy .