***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: The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma , treated with or without enzyme-inducing antiepileptic drug ( EIAED ) therapy  , at the recommended phase 2 dose determined from a previous phase 1 study . Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma ( AG ) or grade IV glioblastoma multiforme ( GBM ) were eligible . No more than one prior chemotherapy was allowed , either as adjuvant therapy or for recurrent disease . The CPT-11 dose was 350 mg/m(2 ) i.v . every three weeks in patients not on EIAED and 750 mg/m(2 ) in patients on EIAED therapy . Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy . The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression , using the rate of six-month progression-free survival ( PFS-6 ) . The trial was sized to be able to discriminate between a 15 % and 35 % rate for the GBM group alone and between a 20 % and 40 % rate for the entire cohort . There were 51 eligible patients , including 38 GBM and 13 AG patients , enrolled . The median age was 52 and 42 years , respectively . PFS-6 for the entire cohort was 17.6 % . PFS-6 was 15.7 % ( 95 % confidence interval [ CI ] , 0.07 - 0.31 ) for the GBM patients and 23 % ( 95 % CI , 0.07 - 0.52 ) for AG patients . Toxicity for the group included diarrhea and myelosuppression . We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule , in this patient population Purpose : Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma , salvage therapies following recurrence offer essentially palliative benefit . We did a phase II trial of bevacizumab , a monoclonal antibody to vascular endothelial growth factor , in combination with irinotecan for patients with recurrent grade 3 malignant glioma . Experimental Design : Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab ( 10 mg/kg ) and irinotecan every 14 days , a second cohort ( n = 24 ) was treated with bevacizumab ( 15 mg/kg ) every 3 weeks with irinotecan on days 1 , 8 , 22 , and 29 of each 42-day cycle . For both cohorts , the dose of irinotecan was 340 mg/m2 for patients on enzyme-inducing antiepileptic drugs ( EIAED ) and 125 mg/m2 for patients not on EIAEDs . After each 6-week cycle , patients were evaluated with a physical examination and magnetic resonance imaging . Results : The 6-month progression-free survival was 55 % ( 95 % confidence interval , 36 - 70 % ) . The 6-month overall survival was 79 % ( 95 % confidence interval , 61 - 89 % ) . Twenty patients ( 61 % ) had at least a partial response . Outcome did not differ between the two treatment cohorts . Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient , and one patient who developed thrombotic thrombocytopenic purpura . Conclusion : Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma PURPOSE Evaluation of treatment effects in malignant brain tumors is challenging because of the lack of reliable response predictors of tumor response . This study examines the predictive value of positron emission tomography ( PET ) using [ 18F ] fluorothymidine ( FLT ) , an imaging biomarker of cell proliferation , in patients with recurrent malignant gliomas treated with bevacizumab in combination with irinotecan .  PATIENTS AND METHODS Patients with recurrent malignant gliomas treated with biweekly cycles of bevacizumab and irinotecan  were prospect ively studied with FLT-PET at baseline , after 1 to 2 weeks , and after 6 weeks from start of treatment . A more than 25 % reduction in tumor FLT uptake as measured by st and ardized uptake value was defined as a metabolic response . FLT responses were compared with response as shown by magnetic resonance imaging ( MRI ) and patient survival . RESULTS Twenty-one patients were included , and 19 were assessable for metabolic response evaluation with FLT-PET . There were nine responders ( 47 % ) and 10 nonresponders ( 53 % ) . Metabolic responders survived three times as long as nonresponders ( 10.8 v 3.4 months ; P = .003 ) , and tended to have a prolonged progression-free survival ( P = .061 ) . Both early and later FLT-PET responses were more significant predictors of overall survival ( 1 to 2 weeks , P = .006 ; 6 weeks , P = .002 ) , compared with the MRI responses ( P = .060 for both 6-week and best responses ) . CONCLUSION FLT-PET as an imaging biomarker seems to be predictive of overall survival in bevacizumab and irinotecan treatment of recurrent gliomas . Whether FLT-PET performed as early as 1 to 2 week after starting treatment is as predictive as the study indicates at 6 weeks warrants further investigation Our objective is to assess treatment efficacy , safety and pattern of response and recurrence in patients with recurrent high- grade glioma treated with bevacizumab and irinotecan .  We review ed retrospectively 51 patients with recurrent high- grade glioma treated with this combination at the Henry Ford Hermelin Brain Tumor Center from 11/15/2005 to 04/01/2008 . The 6-month progression-free survival ( PFS ) for anaplastic gliomas ( AGs ) was 78.6 and 63.7 % for glioblastoma . The median PFS was 13.4 months for AG and 7.6 months for those with glioblastoma . The overall survival rate ( OS ) at 6 months was 85.7 % for AG and 78.0 % for glioblastoma . The 12-month OS was 77.9 % for AG and 42.6 % for glioblastoma . The median OS time for AGs was not reached and was 11.5 months for those with glioblastoma . Thirty-six out of 51 ( 70.59 % ) patients demonstrated partial ( 32/51 ) or complete ( 4/51 ) radiographic response to treatment and 8/51 ( 15.69 % ) remained stable . Of the 38 who demonstrated progression on post-gadolinium studies , 23 showed distant progression with or without local recurrence . Seven patients showed progression on FLAIR without concordant findings on post-Gd sequences . Six patients ( 11.76 % ) discontinued treatment due to a treatment-emergent adverse event , including one with end-stage renal failure and another with gastric perforation . No symptomatic intracranial hemorrhages were reported . Patients with recurrent high- grade glioma treated with bevacizumab plus irinotecan demonstrate an excellent radiographic response rate and improved clinical outcome when compared to historical data . The high rate of distant tumor progression suggests that tumors may adapt to inhibition of angiogenesis by increased infiltration and vascular co-option 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 OF REVIEW To critically assess the role of irinotecan ( Camptosar , CPT-11 ) and bevacizumab ( Avastin ) as a new treatment for glioblastoma and other malignant gliomas ( anaplastic forms of astrocytomas and oligodendrogliomas ) . RECENT FINDINGS Two prospect i ve phase II trials of bevacizumab and irinotecan have been reported . The observed high response rates ( 30 - 60 % ) had never been seen in this disease before . Gains in progression-free survival and overall survival ( OS ) were less impressive ( 6-month progression-free survival 30 - 50 % ; median OS : 9 - 10 months ) , but are still superior to historical controls . SUMMARY Bevacizumab is a welcome new weapon in the treatment of malignant gliomas and should be favored as a salvage treatment over cytotoxic chemotherapy for recurrent disease . However , survival results remain far from satisfactory . Once failure to treatment with bevacizumab is diagnosed by conventional radiographic methods , most patients experience rapid deterioration and die shortly afterward . New methods and radiographic criteria for detecting disease progression are needed . Patients willing to explore new treatment strategies through participation in clinical trials should do so prior to starting bevacizumab , as this may not be an option once treatment fails . Cost-effectiveness of bevacizumab in gliomas deserves further investigation . The role of irinotecan in this combination remains unclear . At this time , bevacizumab should only be used in newly diagnosed malignant gliomas in the setting of a clinical trial 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 6-month overall survival was 57 % ( 95 % CI , 44 % to 75 % ) . Median overall survival was 31 weeks ( 95 % CI , 21 to 54 weeks ) . Early magnetic resonance imaging response ( first 96 hours and 4 weeks ) was predictive of long-term PFS , with the Levin criteria being more predictive than Macdonald criteria . Of 19 patients treated with bevacizumab plus irinotecan at progression , there were no objective radiographic responses . Eighteen patients ( 95 % ) experienced 
    Output:
    
Conclusion The combination of bevacizumab and irinotecan might improve outcome in patients with recurrent malignant glioma .