***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: Summary The purpose of this study was to evaluate by a retrospective analysis of 53 patients the  efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours . The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1 , given by 2-h intravenous infusion , administered every 21 days . Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour . Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients . Among the 11 patients with a well-differentiated tumour evaluable for tumoural response , only one ( 9.4 % ) had a partial response for 8.5 months . Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5 % ( four complete and 13 partial responses ) ; the median duration of response was 9.2 months , the median overall survival 15 months and the median progression-free survival 8.9 months . Haematological grade 3–4 toxicity was observed in 60 % of the cases with one treatment-related death , digestive grade 3–4 toxicity in 40 % and grade 3 alopecia was constant . No severe renal , hearing and neurological toxicities were observed ( grade 1 in 6 % , 14 % , 72 % respectively and no grade > 1 ) . We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination . However , the prognosis remains poor with a 2-year survival lower than 20 % confirming that new therapeutic strategies have to be developed CONTEXT Everolimus , an oral inhibitor of mammalian target of rapamycin , significantly prolongs progression-free survival ( PFS ) in patients with advanced pancreatic neuroendocrine tumors ( pNET ) . Chromogranin A ( CgA ) and neuron-specific enolase ( NSE ) are considered general biomarkers of these tumors . OBJECTIVE The objective of the study was to evaluate the prognostic value of CgA and NSE in patients with pNET treated with everolimus . PATIENTS AND METHODS Patients with low- to intermediate- grade advanced pNET enrolled in two phase 2 studies [ RAD001 in Advanced Neuroendocrine Tumors ( RADIANT-1 ) and single institution phase II study at The University of Texas M. D. And erson Cancer Center ] received  everolimus . Blood sample s were collected and analyzed by a central laboratory at baseline and monthly thereafter . PFS and overall survival ( OS ) were evaluated in patients with elevated and nonelevated baseline CgA/NSE levels . RESULTS In RADIANT-1 , elevated vs. nonelevated baseline CgA was associated with shorter median PFS ( 8.34 vs. 15.64 months ; P = 0.03 ) and OS ( 16.95 months vs. not reached ; P < 0.001 ) . Elevated vs. nonelevated baseline NSE result ed in shorter median PFS ( 7.75 vs. 12.29 months ; P = 0.01 ) and OS ( 13.96 vs. 24.90 months ; P = 0.005 ) . Median PFS was prolonged in patients with early CgA or NSE response ( 11.0 vs. 5.0 months ) compared with those without early biomarker response . More patients with CgA ( 87 vs. 50 % ) or NSE ( 81 vs. 14 % ) response experienced tumor shrinkage compared with those without response . CgA response data from the single-institution phase II study at The University of Texas M. D. And erson Cancer Center study are consistent with data from the RADIANT-1 study . CONCLUSIONS Elevated baseline CgA/NSE provided prognostic information on PFS and survival ; early CgA/NSE responses are potential prognostic markers for treatment outcomes in patients with advanced pNET 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 Pre clinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors . The activity and safety of everolimus was assessed in combination with octreotide long‐acting repeatable ( LAR ) in patients with neuroendocrine tumors ( NETs ) of gastroenteropancreatic and lung origin 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 . ) PURPOSE Despite the fact that most gastroenteropancreatic neuroendocrine tumors ( GEPNETs ) are slow-growing , median overall survival ( OS ) in patients with liver metastases is 2 to 4 years . In metastatic disease , cytoreductive therapeutic options are limited . A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate . Here we report on the toxicity and efficacy of this treatment , performed in over 500 patients . PATIENTS AND METHODS Patients were treated up to a cumulative dose of 750 to 800 mCi ( 27.8 - 29.6 GBq ) , usually in four treatment cycles , with treatment intervals of 6 to 10 weeks .  Toxicity analysis was done in 504 patients , and efficacy analysis in 310 patients . RESULTS Any hematologic toxicity grade 3 or 4 occurred after 3.6 % of administrations . Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients , and temporary , nonfatal , liver toxicity in two patients . Complete and partial tumor remissions occurred in 2 % and 28 % of 310 GEPNET patients , respectively . Minor tumor response ( decrease in size > 25 % and < 50 % ) occurred in 16 % . Median time to progression was 40 months . Median OS from start of treatment was 46 months , median OS from diagnosis was 128 months . Compared with historical controls , there was a survival benefit of 40 to 72 months from diagnosis . CONCLUSION Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects . Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities . Compared with historical controls , there is a benefit in OS from time of diagnosis of several years BACKGROUND & AIMS The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure ( progression , death , stop of study treatment ) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut ( mainly pancreatic ) and midgut tumors . METHODS One hundred nine of 125 registered patients were r and omized starting in January 1995 , and 105 patients ( 51 monotherapy , 54 combination treatment ) were finally analyzed in March 2000 .  Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging .  Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not r and omized because of stable disease . RESULTS Partial tumor regression occurred in 2.9 % , 1.9 % , and 5.7 % and stabilization of tumor growth in 44.8 % , 27.6 % , and 15.2 % at 3 , 6 , and 12 months , respectively , with no significant differences between both treatment arms . In March 2000 , 9.5 % of patients were in treatment . Time to treatment failure and long-term survival did not differ significantly between the 2 groups , with a median survival of 32 and 54 months for the octreotide and the combination groups , respectively . Survival was longer in patients not r and omized because of stable disease ( median , 68 months ) and in those with low nuclear Ki-67 . A trend toward longer survival was shown for patients with slow spontaneous tumor growth before r and omization . Patients responding to treatment lived longer than unresponsive patients . CONCLUSIONS Combination treatment was not superior to monotherapy concerning progression-free and long-term survival . Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage AIM Neuroendocrine tumors over-express somatostatin receptors and literature data have demonstrated the efficacy of the peptide receptor radionuclide therapy with somatostatin analogues labelled with high activities of b-emitting radioisotopes , such as (90)Y and (177)Lu . Yttrium-90 is a pure high energy b-emitter while (177)Lu is a b/g emitter of medium energy . We decided 
    Output:
    
The carcinoid syndrome can be adequately controlled with somatostatin analogs ; chemotherapy has shown positive outcomes in poor prognosis patients , and peptide receptor radionuclide therapy is a promising treatment based on the use of radioisotopes for advanced disease expressing somatostatin receptors .