***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: A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea ( BCNU ) impregnated polymer as theinitial therapy for malignant brain tumors are reported . This is the first study of locally delivered BCNU and st and ard external beam radiation therapy ( XRT ) given concurrently . Twenty-two patients were treated at three hospitals . The entry criteria were : single unilateral tumor focus larger than 1 cm3 ; age over 18 years ; Karnofsky Performance Score ( KPS ) of at least 60 h ; and an intra-operative diagnosis of malignant glioma . Twenty-one of twenty-two patients had glioblastoma multiforme . After surgery , seven or eight BCNU-loaded polyanhydride polymer discs ( 7.7 mg BCNU each ) were placed in the resection cavity . Postoperatively , all patients received st and ard radiation therapy ; none received additional chemotherapy in the first 6 months . Neurotoxicity , systemic toxicity , and survival were assessed . No perioperative mortality was seen . Neurotoxicity was equivalent to that occurring in other series of patients undergoing craniotomy and XRT without local chemotherapy . Systematic ally , no significant bone marrow suppression occurred , and there were no wound infections . Median survival in this group of older patients ( mean age=60 ) was 42 weeks , 8 patients survived 1 year , and 4 patients survived more than 18 months . Interstitial chemotherapy with BCNU-polymer with subsequent radiation therapy appears to be safe as an initial therapy . Several long-term survivors in this group of older patients with predominantly glioblastoma suggests efficacy in some patients . Dose escalation and efficacy trials are planned to further evaluate interstitial chemotherapy for the initial treatment of malignant gliomas OBJECTIVE To find out the effect of carmustine ( bischloroethyl-nitrosourea ) combined with a biodegradable polymer in the treatment of malignant ( Grade s III and IV ) gliomas , applied locally , at the time of the primary operation . METHODS Prospect i ve , r and omized double-blind study of an active treatment group versus a placebo group . Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki , Tampere , and Turku in Finl and and Trondheim in Norway . The study consisted of 32 patients ( 16 in each treatment group ) enrolled between March 23 , 1992 , and March 19 , 1993 . The study was planned to include 100 patients but had to be terminated prematurely , because the drug that was being used had become unobtainable . The main outcome measures included the survival times of patients after the operations and the application of an active drug  or  placebo .  RESULTS The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group ( P = 0.012 ) . For 27 patients with Grade IV tumors , the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group ( P = 0.008 ) . At the end of the study , six patients were still alive , five of whom belonged to the active treatment group . CONCLUSION Carmustine applied locally in a biodegradable polymer at the time of primary operation , seems to have a favorable effect on the life span of patients with high- grade gliomas PURPOSE This New Approaches to Brain Tumor Therapy CNS Consortium study sought to determine the maximum-tolerated dose ( MTD ) of carmustine ( BCNU ) that can be implanted in biodegradable polymers following resection of recurrent high- grade gliomas and the systemic BCNU exposure with increasing doses of interstitial BCNU . PATIENTS AND METHODS Forty-four adults underwent tumor debulking and polymer placement . Six patients per dose level were studied using polymers with 6.5 % , 10 % , 14.5 % , 20 % , and 28 % BCNU by weight . Toxicities were assessed 1 month after implantation by a safety monitoring committee to determine whether subsequent escalations should occur . Nine additional patients were studied at the MTD to confirm safety .  BCNU blood levels were obtained before and after polymer implantation . RESULTS No dose-limiting toxicities were identified at the 6.5 % , 10 % , or 14.5 % dose levels , although difficulties with wound healing , seizures , and brain edema were noted . At the 20 % dose , these effects seemed more prominent , and six additional patients were treated at this dose and tolerated treatment well . Three of four patients receiving the 28 % polymers developed severe brain edema and seizures , and accrual to this cohort was stopped . Nine additional patients received 20 % polymer , confirming this as the MTD . Maximum BCNU plasma concentrations with the 20 % loaded polymers were 27 ng/mL. Overall median survival was 251 days . CONCLUSION The MTD of BCNU delivered in polymer to the surgical cavity is 20 % . This polymer provides five times more BCNU than st and ard commercially available BCNU polymers and results in minimal systemic BCNU exposure . Additional studies are needed to establish the efficacy of high-dose BCNU polymers OBJECTIVE To determine the risks and survival benefit associated with implantation of an absorbable , 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer , we prospect ively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group . METHODS Over a 29-month period , 62 patients underwent operations . All had tumor growth despite st and ard treatment , a Karnofsky performance score of > or = 70 , and histopathological confirmation of glioblastoma . Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers ( wafer group ) at a median 44 weeks from diagnosis ( 6 women , 11 men ; median age , 56 years ) . A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period , but not receiving wafers , was identified . Surgery was performed at a median 47 weeks from diagnosis ( 14 women , 31 men ; median age , 54 years ) . RESULTS Within 6 weeks of surgery , 13 complications were identified in 8 patients in the wafer group . In the cohort group , 6 patients sustained 8 complications . We were unable to identify any survival advantage using Kaplan-Meier analysis . In the wafer group , median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation . In the cohort group , median survival was 97 weeks from diagnosis and 50 weeks from operation . CONCLUSION 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications , particularly those related to infection and wound healing . No clear survival benefit associated with wafer implantation was identified Malignant gliomas have been difficult to treat with chemotherapy . The most effective agent , BCNU ( carmustine ) , has considerable systemic toxicity and a short half-life in serum . To obviate these problems , a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers . Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure . In this Phase I-II study , 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant . Up to eight polymer wafers were placed in the resection cavity intraoperatively , upon completion of tumor debulking . The polymer releases the therapeutic drug for approximately 3 weeks . Three increasing concentrations of BCNU were studied ; the treatment was well tolerated at all three levels . There were no adverse reactions to the BCNU wafer treatment itself . The average survival period after reoperation was 65 weeks for the first dose group , 64 weeks for the second dose group , and 32 weeks for the highest dose group . The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation . The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery . Eighteen ( 86 % ) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight ( 38 % ) of 21 patients lived more than 1 year after intracranial implantation of the polymer . Frequent hematology , blood chemistry , and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy . Since the therapy is well tolerated and safe , a placebo-controlled clinical trial has been started . The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma 
    Output:
    
CONCLUSIONS Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible .
Gliadel is also an option for patients with surgically resectable recurrent malignant glioma