***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: BACKGROUND Recurrent glioblastoma multiforme ( GBM ) is resistant to most therapeutic endeavors , with low response rates and survival rarely exceeding six months . There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life . PATIENTS AND METHODS We report an open-label , uncontrolled , multicenter phase II trial of temozolomide in 138 patients ( intent-to-treat [ ITT ] population ) with glioblastoma multiforme at first relapse and a Karnofsky performance status ( KPS ) > or = 70 . One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma ( GS ) by independent central review . Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle . Patients previously treated with nitrosourea-containing adjuvant chemotherapy  received 150 mg/m2/day for the first five days of a 28-day cycle . In the absence of grade 3 or 4 toxicity , patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle . RESULTS The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria . Secondary endpoints included radiological response and Health-related Quality of Life ( HQL ) . Progression-free survival at six months was 18 % ( 95 % confidence interval ( CI ) : 11%-26 % ) for the eligible-histology population . Median progression-free survival and median overall survival were 2.1 months and 5.4 months , respectively . The six-month survival rate was 46 % . The objective response rate ( complete response and partial response ) determined by independent central review of gadolinium-enhanced magnetic resonance imaging ( MRI ) scans was 8 % for both the ITT and eligible-histology population s , with an additional 43 % and 45 % of patients , respectively , having stable disease ( SD ) . Objective ly assessed response and maintenance of a progression-free status were both associated with HQL benefits ( characterized by improvements over baseline in HQL domains ) . Temozolomide had an acceptable safety profile , with only 9 % of therapy cycles requiring a dose reduction due to thrombocytopenia . There was no evidence of cumulative hematologic toxicity . CONCLUSIONS Temozolomide demonstrated modest clinical efficacy , with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM . The use of this drug should be explored further in an adjuvant setting and in combination with other agents 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 A r and omized , multicentre , open-label , phase II study compared temozolomide ( TMZ ) , an oral second-generation alkylating agent , and procarbazine ( PCB ) in 225 patients with glioblastoma multiforme at first relapse . Primary objectives were to determine progression-free survival ( PFS ) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment . Secondary objectives were to assess overall survival and health-related quality of life ( HRQL ) .  TMZ was given orally at 200 mg/m2/day or 150 mg/m2/day ( prior chemotherapy ) for 5 days , repeated every 28 days . PCB was given orally at 150 mg/m2/day or 125 mg/m2/day ( prior chemotherapy ) for 28 days , repeated every 56 days . HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 [ + 3 ] ) and the Brain Cancer Module 20 ( BCM20 ) . The 6-month PFS rate for patients who received TMZ was 21 % , which met the protocol objective . The 6-month PFS rate for those who received PCB was 8 % ( P = 0.008 , for the comparison ) . Overall PFS significantly improved with TMZ , with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group ( P = 0.0063 ) . The 6-month overall survival rate for TMZ patients was 60 % vs. 44 % for PCB patients ( P = 0.019 ) . Freedom from disease progression was associated with maintenance of HRQL , regardless of treatment received . TMZ had an acceptable safety profile ; most adverse events were mild or moderate in severity . © 2000 Cancer Research One of the objectives of this phase II study was to determine whether temozolomide ( TMZ ) improved the health-related quality of life ( HRQL ) of patients with recurrent anaplastic astrocytoma ( AA ) .  HRQL was assessed at baseline ( pretreatment ) and every 4 weeks at each treatment cycle using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) ( version 2.0 ) and the Brain Cancer Module ( BCM20 ) . Changes from baseline in the scores of seven preselected HRQL domains ( role and social functioning , global QL , visual disorder , motor dysfunction , communication deficit and drowsiness ) were determined at 6 months as well as prior to , and at the time of , disease progression . The significance of the changes was assessed by calculating statistical significance , effect sizes and the proportions of patients with improvement in their HRQL scores ( changes of > /=10 points ) . After 6 months of treatment , patients who were free of progression of disease reported either an improvement or maintenance of all the preselected HRQL domains scores . Patients with disease progression by 6 months usually experienced improvement in HRQL before progression , but there was a sharp decline in most of the preselected domains at progression . We conclude that treatment of recurrent AA with temozolomide is associated with significant HRQL benefits PURPOSE To determine whether chemotherapy with temozolomide ( TMZ ) versus procarbazine ( PCB ) for recurrent glioblastoma multiforme ( GBM ) was associated with improvement in health-related quality of life ( HRQOL ) . PATIENTS AND METHODS HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 and a Brain Cancer Module ( BCM20 ) in two clinical trials that enrolled a total of 366 patients . Two hundred eighty-eight patients provided HRQOL data that could be used for analysis ; 109 patients received TMZ  in a phase II study , whereas 89 patients received TMZ  and 90 received  PCB in a r and omized phase III study . Changes from baseline in the scores of seven preselected HRQOL domains ( role and social functioning , global quality of life [ QOL ] , visual disorders , motor dysfunction , communication deficit , and drowsiness ) were calculated for all groups . Statistical significance , effect sizes , and proportions of patients with improved HRQOL scores ( changes of > or = 10 points ) were calculated . RESULTS Before disease progression , patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline ( pretreatment ) scores . Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains . Conversely , patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months . Patients with disease progression , regardless of treatment , experienced a sharp decline in all domains at the time of progression . CONCLUSION Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB . The deterioration reported by PCB-treated patients was likely because of toxicity . Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM Temozolomide , a new oral cytotoxic agent , was given to 75 patients with malignant gliomas . The schedule used was for the first course 150 mg/m2 per day for 5 days ( i.e. total dose 750 mg/m2 ) , escalating , if no significant myelosuppression was noted on day 22 , to 200 mg/m2 per day for 5 days ( i.e. total dose 1000 mg/m2 ) for subsequent courses at 4-week intervals . There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 ( 30 % ) fulfilled the criteria for an objective response . There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 ( 25 % ) fulfilled the criteria for an objective response . This gave an overall objective response rate of 20 ( 27 % ) out of 75 patients . Temozolomide was generally well tolerated , with little subjective toxicity and predictable myelosuppression . However , the responses induced with this schedule were of short duration and had relatively little impact on overall survival . In conclusion , temozolomide given in this schedule has activity against high grade glioma . However , studies evaluating chemotherapy in primary brain tumours should include a quality -of-life/performance status evaluation in addition to CT or MRI scanning assessment 
    Output:
    
The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival .
Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life .
Overall the evidence -base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide .