***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: PURPOSE Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma ( GBM ) by increasing the therapeutic index , overcoming common mechanisms of temozolomide resistance , or both . The goal of this r and omized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM . PATIENTS AND METHODS Adult patients with newly diagnosed GBM were r and omly assigned to receive st and ard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense ( 150 mg/m(2 ) days 1 to 7 and 15 to 21 ) or metronomic ( 50 mg/m(2 ) continuous daily ) temozolomide . Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression . The primary end point was overall survival ( OS ) at 1 year . Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status . RESULTS Eighty-five eligible patients were enrolled ; 42 were r and omly assigned to dose-dense and 43 to metronomic temozolomide . The 1-year survival rate was 80 % for the dose-dense arm and 69 % for the metronomic arm ; median OS was 17.1 months ( 95 % CI , 14.0 to 28.1 months ) and 15.1 months ( 95 % CI , 12.3 to 18.9 months ) , respectively . The most common toxicities were myelosuppression ( leukopenia , neutropenia , and thrombocytopenia ) and elevated liver enzymes . Pseudoprogression was observed in 37 % of assessable patients and may have had an impact on estimates of progression-free survival ( 6.6 months in the dose-dense arm and 5.0 months in the metronomic arm ) . CONCLUSION Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity . The dose-dense regimen appears promising , with 1-year survival of 80 % PURPOSE Approximately 50 % of glioblastomas ( GBMs ) are characterized by overexpression of the epidermal growth factor receptor ( EGFR ) and EGFR gene amplification . In approximately 25 % of instances , constitutively activated EGFR mutants are present . These observations make EGFR-inhibiting drugs a logical approach for trials in recurrent GBM . PATIENTS AND METHODS In a r and omized , controlled , phase II trial , 110 patients with progressive GBM after prior radiotherapy were r and omly assigned to either erlotinib or a control arm that received treatment with either temozolomide or carmustine ( BCNU ) . The primary end point was 6-month progression-free survival ( PFS ) . Tumor specimens obtained at first surgery were investigated for EGFR expression ; EGFRvIII mutants ; EGFR amplification ; EGFR mutations in exons 18 , 19 , and 21 ; and pAkt . These results were correlated with outcome . Pharmacokinetic analysis was part of the study . RESULTS ; Treatment was well tolerated in general ; skin toxicity was the most frequent adverse effect of erlotinib . The 6-month PFS rate in the erlotinib arm was 11.4 % ( 95 % CI , 4.6 % to 21.5 % ) , and it was 24 % in the control arm . Of all explored biomarkers , only low pAkt expression appeared to be of borderline significance to an improved outcome . None of the eight patients who had tumors with EGFRvIII mutant presence and PTEN expression had 6-month PFS . The use of enzyme-inducing anticonvulsants significantly increased erlotinib clearance , but pharmacokinetic findings were not related to outcome . CONCLUSION Erlotinib has insufficient single-agent activity in unselected GBM . No clear biomarker associated with improved outcome to erlotinib was identified A prospect i ve r and omized controlled multicenter phase III trial was conducted to evaluate the effects of neoadjuvant chemotherapy with nimustine (ACNU)-cisplatin ( CDDP ) when used in conjunction with radiotherapy plus adjuvant temozolomide in patients with newly diagnosed glioblastoma . The study population was r and omly assigned into one treatment and one control group . Both groups received radiotherapy followed by six cycles of adjuvant oral temozolomide ( 150–200 mg/m2 ) for 5 days every 28 days after surgery . Prior to radiotherapy , the treatment group also received two cycles , 6 weeks apart , of neoadjuvant chemotherapy with ACNU ( 40 mg/m2/day ) and CDDP ( 40 mg/m2/day ) infused continuously for 72 h. The primary end-point was median survival time . The study has closed after interim analysis with a total of 82 patients ( 48.8 % of target number ) due to unacceptable high frequency of toxicity profiles in spite of the promising actuarial survival outcome . Median survival time was 28.4 months [ 90 % confidence interval ( CI ) , 21.1 months to not available ] in the treatment group and 18.9 months ( 90 % CI , 17.1–27.4 months ) in the control group ( P = 0.2 ) . The 2-year survival rate and progression-free survival time were 50.9 % and 6.6 months ( 90 % CI , 3.5–9.5 months ) in the treatment group and 27.8 % and 5.1 months ( 90 % CI , 3.8–8.8 months ) in the control group . Grade 3 or 4 toxicity was documented in 26 ( 68.4 % ) patients in the treatment group , including three neutropenic fever and one death from sepsis , while grade 3 or 4 toxicity occurred in 6 patients ( 15.8 % ) in the control group . The high frequency of serious hematological toxicity with ACNU-CDDP neoadjuvant chemotherapy followed by radiotherapy and adjuvant temozolomide limits its usage as primary treatment for glioblastoma . Future studies should aim to identify a sub population at reduced risk for ACNU-CDDP toxicity so that the potential of this protocol can be realized Purpose : Patients with progressive or recurrent supratentorial high- grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide . Methods : The treatment schedule was 150–200 mg/m2 per day orally for 5 days repeated every 28 days . Response evaluation was by a combination of  neurological status evaluation ( MRC scale ) and imaging .  Results : Of 103 eligible patients enrolled , 11 ( 11 % ) achieved an objective response and a further 48 ( 47 % ) had stable disease . The median response duration was 4.6 months . Response rates were similar for anaplastic astrocytomas ( grade III ) and glioblastoma multiforme ( grade IV ) tumours . Predictable myelosuppression was the major toxicity . Conclusions : The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high- grade gliomas PURPOSE To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse . PATIENTS AND METHODS This open-label , multicenter , phase II trial enrolled 162 patients ( intent-to-treat [ ITT ] population ) . After central histologic review , 111 patients were confirmed to have had an anaplastic astrocytoma ( AA ) or anaplastic mixed oligoastrocytoma . Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d . Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d ; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity . Therapy was administered orally on the first 5 days of a 28-day cycle . RESULTS Progression-free survival ( PFS ) at 6 months , the primary protocol end point , was 46 % ( 95 % confidence interval , 38 % to 54 % ) . The median PFS was 5.4 months , and PFS at 12 months was 24 % . The median overall survival was 13.6 months , and the 6- and 12-month survival rates were 75 % and 56 % , respectively . The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35 % ( 8 % complete response [ CR ] , 27 % partial response [ PR ] ) , with an additional 26 % of patients with stable disease ( SD ) . The median PFS for patients with SD was 4.4 months , with 33 % progression-free at 6 months . Maintenance of progression-free status and objective ly assessed response ( CR/PR/SD ) were both associated with health-related quality -of-life ( HQL ) benefits . Adverse events were mild to moderate , with hematologic side effects occurring in less than 10 % of patients . CONCLUSION Temozolomide demonstrated good single-agent activity , an acceptable safety profile , and documented HQL benefits in patients with recurrent AA PURPOSE Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor ( VEGF ) with demonstrated efficacy in combination with carboplatin and paclitaxel ( PCB ) for the treatment of advanced non-small-cell lung cancer ( NSCLC ) . Administration of bevacizumab is postulated to decrease nitric oxide synthesis and lead to hypertension , which may be a physiological sign that the VEGF pathway is more actively being blocked and could result in improved outcomes . PATIENTS AND METHODS Eastern Cooperative Oncology Group ( ECOG ) 4599 r and omly assigned patients with nonsquamous NSCLC to carboplatin and paclitaxel ( PC ) versus PCB .  Hypertensive patients were compared with nonhypertensive patients with respect to overall survival ( OS ) and progression-free survival ( PFS ) using blood pressure data and adverse event data separately . High blood pressure ( HBP ) by the end of cycle 1 was defined as blood pressure > 150/100 at any previous time or at least a 20-mmHg increase in diastolic blood pressure from baseline . Results In a multivariable Cox model adjusting for HBP as a time-varying covariate , comparing those on PCB with HBP with those on PC gave an OS hazard ratio ( HR ) of 0.60 ( 95 % CI , 0.43 to 0.81 ; P = .001 ) ; comparing those on PCB without HBP with those on PC alone , the OS HR was 0.86 ( 95 % CI , 0.74 to 1.00 ; P = .05 ) . Comparing the PCB HBP group with PC gave an adjusted PFS HR of 0.54 ( 95 % CI , 0.41 to 0.73 ; P < .0001 ) and comparing those on PCB without HBP to those on PC , the HR was 0.72 ( 95 % CI , 0.62 to 0.84 ; P < .0001 ) . The 6-month cumulative incidence of hypertension was 6.2 % ( 95 % CI , 3.9 % to 8.6 % ) . CONCLUSION Data from ECOG 4599 suggest that onset of HBP during treatment with PCB may be associated with improved outcomes , and additional studies of the downstream effects of VEGF suppression and hypertension are needed This r and omized , open-label , active-controlled , dose-finding phase IIb study evaluated the efficacy and safety of trabedersen ( AP 12009 ) administered intratumorally by convection-enhanced delivery compared with st and ard chemotherapy in patients with recurrent/refractory high- grade glioma . One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) were r and omly assigned to receive trabedersen at doses of 10 or 80 µM or st and ard chemotherapy ( temozolomide or procarbazine/lomustine/vincristine ) . Primary endpoint was 6-month tumor control rate , and secondary endpoints included response at further timepoints , survival , and safety . Six-month tumor control rates were not significantly different in the entire study population ( AA and GBM ) . Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 µM trabedersen vs chemotherapy ( p= .0032 ) . The 2-year survival rate had a trend for superiority for 10 µM trabedersen vs chemotherapy ( p = .10 ) . Median survival for 10 µM trabedersen was 39.1 months compared with 35.2 months for 80 µM trabedersen and 21.7 months for chemotherapy ( not significant ) . In GBM  patients , response and survival results were comparable among the 3 arms . Exploratory analysis on GBM patients aged ≤55 years with Karnofsky performance status > 80 % at 
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A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications , fatigue and infections were increased with temozolomide .
In the elderly , 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone .
QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide .
Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone .
It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events .
In recurrent GBM , temozolomide compared with st and ard chemotherapy improves time-to-progression ( TTP ) and may have benefits on QoL without increasing adverse events but it does not improve overall .
In the elderly , temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events