***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 : 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 The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation 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 BACKGROUND Oligodendroglial tumors are chemosensitive , with two-thirds of patients responding to PCV combination chemotherapy with procarbazine , lomustine ( CCNU ) and vincristine . Temozolomide ( TMZ ) , a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma . We investigated this drug in recurrent oligodendroglial tumors ( OD ) and mixed oligoastrocytomas ( OA ) after prior PCV chemotherapy and radiation therapy . PATIENTS AND METHODS In a prospect i ve non-r and omized multicenter phase II trial patients were treated with TMZ 150 mg/m(2 ) on days 1 - 5 in cycles of 28 days for 12 cycles . Eligible patients had a recurrence after prior PCV chemotherapy , with measurable and enhancing disease as shown by magnetic resonance imaging . Pathology and all responses were central ly review ed . RESULTS Thirty-two eligible patients were included . In four patients the pathology review did not confirm the presence of an OD or OA . Twelve of 24 patients [ 50 % , 95 % confidence interval ( CI ) 29 % to 71 % ] evaluable for response to first-line PCV chemotherapy had responded to PCV . Temozolomide  was in general well tolerated ; the most frequent side-effects were hematological . One patient discontinued treatment due to toxicity . In seven of 28 patients ( 25 % , 95 % CI 11 % to 45 % ) with histologically confirmed OD an objective response to TMZ was observed . Median time to progression for responding patients was 8.0 months . After 6 and 12 months from the start of treatment , 29 % and 11 % of patients , respectively , were still free from progression . CONCLUSIONS TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy . Further studies on TMZ in OD are indicated The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma . The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36 . Four of the 24 patients responded ( 17 % ) . Fifty percent of patients were still free from progression at 6 months and 21 % were free from progression at 12 months . Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy , this relation was absent in salvage PCV chemotherapy PURPOSE Temozolomide ( TMZ ) is an alkylating agent licensed for treatment of high- grade glioma ( HGG ) . No prospect i ve comparison with nitrosourea-based chemotherapy exists . We report , to our knowledge , the first r and omized trial of procarbazine , lomustine , and vincristine ( PCV ) versus TMZ in chemotherapy-naive patients with recurrent HGG . PATIENTS AND METHODS Four hundred forty-seven patients were r and omly assigned to PCV ( 224 patients ) or TMZ ( sub-r and om assignment : TMZ-5 [ 200 mg/m(2 ) for 5 days , 112 patients ] or TMZ-21 [ 100 mg/m(2 ) for 21 days , 111 patients ] ) for up to 9 months or until progression . The primary outcomes were survival ( PCV v TMZ ) and 12-week progression-free survival ( PFS ; TMZ-5 v TMZ-21 ) . This study is registered as IS RCT N83176944 . RESULTS Percentages of patients completing 9 months of treatment in the PCV , TMZ-5 , and TMZ-21 arms were 17 % , 26 % , and 13 % , respectively . Major toxicity was similar across all three groups . With a median follow-up time of 12 months and 382 deaths , there was no clear survival benefit when comparing PCV with TMZ ( hazard ratio [ HR ] , 0.91 ; 95 % CI , 0.74 to 1.11 ; P = .350 ) . For TMZ-5 versus TMZ-21 , 12-week PFS rates were similar ( 63.6 % and 65.7 % , respectively ; P = .745 ) , but TMZ-5 improved overall PFS ( HR , 1.38 ; 95 % CI , 1.05 to 1.82 ; P = .023 ) , survival ( HR , 1.32 ; 95 % CI , 0.99 to 1.75 ; P = .056 ) , and global quality of life ( 49 % v 19 % improved > 10 points at 6 months , respectively ; P = .005 ) . CONCLUSION Although TMZ ( both arms combined ) did not show a clear benefit compared with PCV , comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting . This challenges the current underst and ing of increasing TMZ dose-intensity by prolonged scheduling PURPOSE Anaplastic oligodendroglioma are chemotherapy-sensitive tumors . We now present the long-term follow-up findings of a r and omized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial tumors were r and omly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV . An exploratory analysis of the correlation between 1p/19q status and survival was part of the study . Retrospectively , the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase ( IDH ) gene were determined . The primary end points were overall survival ( OS ) and progression-free survival based on intent-to-treat analysis . RESULTS A total of 368 patients were enrolled . With a median follow-up of 140 months , OS in the RT/PCV arm was significantly longer ( 42.3 v 30.6 months in the RT arm , hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.60 to 0.95 ) . In the 80 patients with a 1p/19q codeletion , OS was increased , with a trend toward more benefit from adjuvant PCV ( OS not reached in the RT/PCV group v 112 months in the RT group ; HR , 0.56 ; 95 % CI , 0.31 to 1.03 ) . IDH mutational status was also of prognostic significance . CONCLUSION The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors . 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) plus recombinant interferon-alpha ( IFN-alpha ) in patients with recurrent glioma . As single agents , both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma . In vitro studies suggest synergy between the two agents . Thirty-five patients in whom computerized tomography ( CT ) or magnetic resonance ( MR ) evidence was obtained of progressive astrocytoma , oligoastrocytoma , or oligodendroglioma received recombinant IFN-alpha 2a 
    Output:
    
Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes .
Adverse events are similar and QoL scores are statistically but not clinical ly significant between TMZ and PCV .