***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: Single-agent sunitinib , an oral small molecule inhibitor of multiple tyrosine kinase receptors , was evaluated for treatment of patients with recurrent glioblastoma ( GB ) and anaplastic astrocytoma ( AA ) . Fourteen AA and 16 GB patients , all previously treated with surgery , radiotherapy , and temozolomide , were enrolled in a prospect i ve phase II study at either first or second relapse . Patients were treated with daily sunitinib for 4 consecutive weeks , followed by a 2-week break . For AA patients , the most common side effects were fatigue ( 86 % ) , diarrhea ( 43 % ) , h and -foot syndrome ( 36 % ) , neutropenia ( 36 % ) , thrombocytopenia ( 36 % ) , and nausea ( 29 % ) . In the GB cohort , the most common side effects were fatigue ( 56 % ) , diarrhea ( 44 % ) , neutropenia ( 31 % ) , and thrombocytopenia ( 25 % ) . Six of 14 ( 43 % ) AA and 5 of 16 ( 31 % ) GB patients experienced grade 3 or greater toxicities . Five patients discontinued study due to drug toxicities . There were no partial or complete responses in either cohort ; 8/14 ( 57 % ) AA and 5/16 ( 31 % ) GB patients had stable disease at the first planned assessment . Progression-free survival at 6 months was 21.5 % ( AA ) and 16.7 % ( GB ) . Median overall survival was 12.1 months ( AA ) and 12.6 months ( GB ) . These results are comparable to those reported in the literature in patients treated with st and ard cytotoxic therapies . This is the largest reported trial of sunitinib in recurrent malignant astrocytic gliomas to date , as well as contains the largest AA cohort . Nonetheless , sunitinib did not demonstrate significant anti-glioma activity in patients with recurrent malignant astrocytic gliomas The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative , S-1 , in patients receiving initial chemotherapy for unresectable , advanced non-small-cell lung cancer ( NSCLC ) . Between June 1996 and July 1998 , 62 patients with NSCLC who received no previous chemotherapy for advanced disease were enrolled in this study . Fifty nine patients ( 22 in stage IIIB and 37 in stage IV ) were eligible for the evaluation of efficacy and safety .  S-1 was orally administered twice daily after meals . Three doses of S-1 were prescribed according to body surface area ( BSA ) , so that they would be approximately equivalent to 80 mg/m2/day . One cycle of S-1 consisted of consecutive administration for 28 days followed by a 2-week rest , and the cycle was repeated up to 4 times . The partial response ( PR ) rate of the eligible patients was 22.0 % ( 13/59 ) ( 95 % confidence interval : 12.3 - 34.7 % ) . Grade 4 neutropenia was observed in one of the 59 patients ( 1.7 % ) . There were no irreversible , severe or unexpected toxicities . The median survival time ( MST ) of all of the patients was 10.2 months ( 95 % confidence interval : 7.7 - 14.5 months ) , and the one-year survival rate was 41.1 % . S-1 was considered to be an active single agent against NSCLC BACKGROUND Treatment options for recurrent glioblastoma are scarce , with second-line chemotherapy showing only modest activity against the tumour . Despite the absence of well controlled trials , bevacizumab is widely used in the treatment of recurrent glioblastoma . Nonetheless , whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear . We report the results of the first r and omised controlled phase 2 trial of bevacizumab in recurrent glioblastoma . METHODS The BELOB trial was an open-label , three-group , multicentre phase 2 study undertaken in 14 hospitals in the Netherl and s. Adult patients ( ≥18 years of age ) with a first recurrence of a glioblastoma after temozolomide chemoradiotherapy  were r and omly allocated by a web-based program to treatment with oral lomustine 110 mg/m(2 ) once every 6 weeks , intravenous bevacizumab 10 mg/kg once every 2 weeks , or combination treatment with lomustine 110 mg/m(2 ) every 6 weeks and bevacizumab 10 mg/kg every 2 weeks . R and omisation of patients was stratified with a minimisation procedure , in which the stratification factors were centre , Eastern Cooperative Oncology Group performance status , and age . The primary outcome was overall survival at 9 months , analysed by intention to treat . A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination treatment group . This trial is registered with the Nederl and s Trial Register ( www.trialregister.nl , number NTR1929 ) . FINDINGS Between Dec 11 , 2009 , and Nov 10 , 2011 , 153 patients were enrolled . The preplanned safety analysis was done after eight patients had been treated , because of haematological adverse events ( three patients had grade 3 thrombocytopenia and two had grade 4 thrombocytopenia ) which reduced bevacizumab dose intensity ; the lomustine dose in the combination treatment group was thereafter reduced to 90 mg/m(2 ) . Thus , in addition to the eight patients who were r and omly assigned to receive bevacizumab plus lomustine 110 mg/m(2 ) , 51 patients were assigned to receive bevacizumab alone , 47 to receive lomustine alone , and 47 to receive bevacizumab plus lomustine 90 mg/m(2 ) . Of these patients , 50 in the bevacizumab alone group , 46 in the lomustine alone group , and 44 in the bevacizumab and lomustine 90 mg/m(2 ) group were eligible for analyses . 9-month overall survival was 43 % ( 95 % CI 29 - 57 ) in the lomustine group , 38 % ( 25 - 51 ) in the bevacizumab group , 59 % ( 43 - 72 ) in the bevacizumab and lomustine 90 mg/m(2 ) group , 87 % ( 39 - 98 ) in the bevacizumab and lomustine 110 mg/m(2 ) group , and 63 % ( 49 - 75 ) for the combined bevacizumab and lomustine groups . After the reduction in lomustine dose in the combination group , the combined treatment was well tolerated . The most frequent grade 3 or worse toxicities were hypertension ( 13 [ 26 % ] of 50 patients in the bevacizumab group , three [ 7 % ] of 46 in the lomustine group , and 11 [ 25 % ] of 44 in the bevacizumab and lomustine 90 mg/m(2 ) group ) , fatigue ( two [ 4 % ] , four [ 9 % ] , and eight [ 18 % ] ) , and infections ( three [ 6 % ] , two [ 4 % ] , and five [ 11 % ] ) . At the time of this analysis , 144/148 ( 97 % ) of patients had died and three ( 2 % ) were still on treatment . INTERPRETATION The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies . However , the results in the bevacizumab alone group do not justify further studies of this treatment . FUNDING Roche Nederl and and KWF Kankerbestrijding AIMS Many elderly glioblastoma patients are excluded from r and omised trials due to age , comorbidity or poor functional status . The purpose of this study was to describe the survival outcomes in all elderly patients with glioblastoma managed at a tertiary cancer centre . MATERIAL S AND METHODS A retrospective chart review identified 235 elderly patients ( age 65 years or over ) with a histological diagnosis of glioblastoma between 1 December 2006 and 31 December 2013 . The primary outcome of this study was overall survival by treatment type . Univariate and multivariate Cox proportional hazard models were used to explore significant prognostic variables associated with overall survival . RESULTS The median survival for all patients was 6.5 months ( 95 % confidence interval 5.3 - 7.7 ) , with 1 year overall survival of 23.7 % ( 95 % confidence interval 18.8 - 30.0 ) . The median survival for patients treated with radiation and chemotherapy was 11.1 months ( 95 % confidence interval 8.1 - 13.7 ) . Patients treated with radiation alone had a median survival of 6.8 months ( 95 % confidence interval 5.6 - 7.9 ) . For patients managed with comfort measures only , the median survival was 1.9 months ( 95 % confidence interval 1.6 - 2.6 ) . Univariate analysis revealed age , performance status , surgery type ( biopsy , subtotal resection , gross total resection ) and type of treatment received  ( comfort measures only , radiotherapy alone , radiotherapy and chemotherapy ) to be statistically associated with overall survival . In the multivariate analysis , only two predictive factors ( treatment received and surgery type ) were significant . CONCLUSIONS Elderly patients with glioblastoma selected for treatment ( surgery followed by radiation alone or radiation and chemotherapy )  survive longer than patients managed with comfort measures . Prospect i ve r and omised trials will help guide management for patients eligible for therapy . Elderly patients with glioblastoma who are deemed not eligible for active therapy have very short survival Purpose : Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy . This study was conducted to determine if the combination of a novel antiangiogenic therapy , bevacizumab , and a cytotoxic agent , irinotecan , is safe and effective for patients with recurrent grade III-IV glioma . Experimental Design : We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma . Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded . Patients were scheduled to receive bevacizumab and irinotecan i.v . every 2 weeks of a 6-week cycle . Bevacizumab was administered at 10 mg/kg . The dose of irinotecan was determined based on antiepileptic use : patients taking enzyme-inducing antiepileptic drugs received 340 mg/m2 , whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m2 . Toxicity and response were assessed . Results : Thirty-two patients were assessed ( 23 with grade IV glioma and 9 with grade III glioma ) .  Radiographic responses were noted in 63 % ( 20 of 32 ) of patients ( 14 of 23 grade IV patients and 6 of 9 grade III patients ) . The median progression-free survival was 23 weeks for all patients ( 95 % confidence interval , 15 - 30 weeks ; 20 weeks for grade IV patients and 30 weeks for grade III patients ) . The 6-month progression-free survival probability was 38 % and the 6-month overall survival probability was 72 % . No central nervous system hemorrhages occurred , but three patients developed deep venous thromboses or pulmonary emboli , and one patient had an arterial ischemic stroke . Conclusions : The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity PURPOSE To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma . PATIENTS AND METHODS Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks . After tumor progression , patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2 ) or 125 mg/m(2 ) every 2 weeks , depending on use of enzyme-inducing antiepileptic drugs . Complete patient evaluations were repeated every 4 weeks . RESULTS Forty-eight heavily pretreated patients were accrued to this study .  Thromboembolic events ( 12.5 % ) , hypertension ( 12.5 % ) , hypophosphatemia ( 6 % ) , and thrombocytopenia ( 6 % ) were the most common drug-associated adverse events . Six patients ( 12.5 % ) were removed from study for drug-associated toxicity ( five thromboembolic events , one bowel perforation ) . Thirty-four patients ( 71 % ) and 17 patients ( 35 % ) achieved radiographic response based on Levin and Macdonald criteria , respectively . Median progression-free survival ( PFS ) was 16 weeks ( 95 % CI , 12 to 26 weeks ) . The 6-month PFS was 29 % ( 95 % CI , 18 % to 48 % ) . The  
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In comparison with other angiogenesis inhibitors and thalidomide , the use of single agent bevacizumab as salvage treatment for recurrent GBM patients improve ORR and 6-months PFS , but not for 1-year OS