Cisplatinum and BCNU chemotherapy in primary glioblastoma patients
Background The prognosis of patients with glioblastoma is very poor with a mean survival of 10–12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma mu...
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| Veröffentlicht in: | Journal of neuro-oncology 2009-08, Vol.94 (1), p.57-62 |
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| creator | Silvani, Antonio Gaviani, Paola Lamperti, Elena A. Eoli, Marica Falcone, Chiara DiMeco, Francesco Milanesi, Ida M. Erbetta, Alessandra Boiardi, Amerigo Fariselli, Laura Salmaggi, Andrea |
| description | Background
The prognosis of patients with glioblastoma is very poor with a mean survival of 10–12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients. Methylated methylguanine methyltransferase (
MGMT
) promoter is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome
MGMT
-mediated chemoresistance are being actively investigated.
Methods
A retrospective analysis on 160 adult patients (≥16 years) treated for histologically confirmed GBM between 2003 and 2005 at our Institution was performed. All patients were treated with conventional fractionated radiotherapy and a combined chemotherapy treatment with Cisplatin (CDDP) (100 mg/sqm on day 1) and carmustine (BCNU) (160 mg/sqm on day 2); the treatment was repeated every 6 weeks for five cycles. Toxicity, progression free survival and overall survival were assessed.
Results
The median number of chemotherapy cycles delivered to each patient was 5 (range 3–6), with no patients discontinuing treatment because of refusal or toxicity. Dose reduction was required in 16 patients (10%), and all patients completed radiotherapy, whereas 5 patients discontinued chemotherapy before completing all planned cycles for disease progression. The primary toxicities were: neutropenia (grade 3–4: 23%), thrombocytopenia (grade 3–4: 18.5%), and nausea and vomiting (13%). Median progression-free survival times and 1-year progression free survival were 7.6 months (95% CI 6.6–8.5) and 17.3%, respectively. OS was 15.6 months (95% CI 14.1–17.1).
Conclusions
Our results for PFS and overall survival are comparable with those obtained with temozolomide, but the toxicity occurring in our series was more frequent and persistent. The toxicity, and mainly the modalities of administration associated with cisplatin and BCNU combination, argues against future use in the treatment of patients with GBM. |
| doi_str_mv | 10.1007/s11060-009-9800-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_20227402</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1776916281</sourcerecordid><originalsourceid>FETCH-LOGICAL-c400t-4f4deaab88dcc584505749ed230264982a3bcf3ffa10675d166a18bc9625899c3</originalsourceid><addsrcrecordid>eNp1kMtKxDAUhoMozjj6AG6kuHBXPbk1zVKLNxh044C7kKbpTIfeTNrFvL0ZOjAguEog3__nnA-hawz3GEA8eIwhgRhAxjKFcDlBc8wFjQUV9BTNASci5pJ9z9CF91sAYILiczTDkmAigM3RU1b5vtZD1Y5NpNsieso-VpHZ2KYbNtbpfhdVbdS7qtFuF63rqstr7Yeu0VEfUrYd_CU6K3Xt7dXhXKDVy_NX9hYvP1_fs8dlbBjAELOSFVbrPE0LY3jKOHDBpC0IBZIwmRJNc1PSstRhKcELnCQap7mRCeGplIYu0N3U27vuZ7R-UE3lja1r3dpu9IoAIYIBCeDtH3Dbja4NsymCJZeYQBIgPEHGdd47W6rDkgqD2ttVk10V7Kq9XQUhc3MoHvPGFsfEQWcAyAT48NSurTv-_H_rL52lg7w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>219591206</pqid></control><display><type>article</type><title>Cisplatinum and BCNU chemotherapy in primary glioblastoma patients</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Silvani, Antonio ; Gaviani, Paola ; Lamperti, Elena A. ; Eoli, Marica ; Falcone, Chiara ; DiMeco, Francesco ; Milanesi, Ida M. ; Erbetta, Alessandra ; Boiardi, Amerigo ; Fariselli, Laura ; Salmaggi, Andrea</creator><creatorcontrib>Silvani, Antonio ; Gaviani, Paola ; Lamperti, Elena A. ; Eoli, Marica ; Falcone, Chiara ; DiMeco, Francesco ; Milanesi, Ida M. ; Erbetta, Alessandra ; Boiardi, Amerigo ; Fariselli, Laura ; Salmaggi, Andrea</creatorcontrib><description>Background
The prognosis of patients with glioblastoma is very poor with a mean survival of 10–12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients. Methylated methylguanine methyltransferase (
MGMT
) promoter is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome
MGMT
-mediated chemoresistance are being actively investigated.
Methods
A retrospective analysis on 160 adult patients (≥16 years) treated for histologically confirmed GBM between 2003 and 2005 at our Institution was performed. All patients were treated with conventional fractionated radiotherapy and a combined chemotherapy treatment with Cisplatin (CDDP) (100 mg/sqm on day 1) and carmustine (BCNU) (160 mg/sqm on day 2); the treatment was repeated every 6 weeks for five cycles. Toxicity, progression free survival and overall survival were assessed.
Results
The median number of chemotherapy cycles delivered to each patient was 5 (range 3–6), with no patients discontinuing treatment because of refusal or toxicity. Dose reduction was required in 16 patients (10%), and all patients completed radiotherapy, whereas 5 patients discontinued chemotherapy before completing all planned cycles for disease progression. The primary toxicities were: neutropenia (grade 3–4: 23%), thrombocytopenia (grade 3–4: 18.5%), and nausea and vomiting (13%). Median progression-free survival times and 1-year progression free survival were 7.6 months (95% CI 6.6–8.5) and 17.3%, respectively. OS was 15.6 months (95% CI 14.1–17.1).
Conclusions
Our results for PFS and overall survival are comparable with those obtained with temozolomide, but the toxicity occurring in our series was more frequent and persistent. The toxicity, and mainly the modalities of administration associated with cisplatin and BCNU combination, argues against future use in the treatment of patients with GBM.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-009-9800-0</identifier><identifier>PMID: 19212704</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Antineoplastic Agents - therapeutic use ; Brain Neoplasms - drug therapy ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain Neoplasms - radiotherapy ; Carmustine - therapeutic use ; Cisplatin - therapeutic use ; Clinical Study-Patient Study ; Combined Modality Therapy ; Dose-Response Relationship, Drug ; Female ; Glioblastoma - drug therapy ; Glioblastoma - mortality ; Glioblastoma - pathology ; Glioblastoma - radiotherapy ; Humans ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Neurology ; Oncology ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Young Adult</subject><ispartof>Journal of neuro-oncology, 2009-08, Vol.94 (1), p.57-62</ispartof><rights>Springer Science+Business Media, LLC. 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-4f4deaab88dcc584505749ed230264982a3bcf3ffa10675d166a18bc9625899c3</citedby><cites>FETCH-LOGICAL-c400t-4f4deaab88dcc584505749ed230264982a3bcf3ffa10675d166a18bc9625899c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11060-009-9800-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11060-009-9800-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19212704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Silvani, Antonio</creatorcontrib><creatorcontrib>Gaviani, Paola</creatorcontrib><creatorcontrib>Lamperti, Elena A.</creatorcontrib><creatorcontrib>Eoli, Marica</creatorcontrib><creatorcontrib>Falcone, Chiara</creatorcontrib><creatorcontrib>DiMeco, Francesco</creatorcontrib><creatorcontrib>Milanesi, Ida M.</creatorcontrib><creatorcontrib>Erbetta, Alessandra</creatorcontrib><creatorcontrib>Boiardi, Amerigo</creatorcontrib><creatorcontrib>Fariselli, Laura</creatorcontrib><creatorcontrib>Salmaggi, Andrea</creatorcontrib><title>Cisplatinum and BCNU chemotherapy in primary glioblastoma patients</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>Background
The prognosis of patients with glioblastoma is very poor with a mean survival of 10–12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients. Methylated methylguanine methyltransferase (
MGMT
) promoter is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome
MGMT
-mediated chemoresistance are being actively investigated.
Methods
A retrospective analysis on 160 adult patients (≥16 years) treated for histologically confirmed GBM between 2003 and 2005 at our Institution was performed. All patients were treated with conventional fractionated radiotherapy and a combined chemotherapy treatment with Cisplatin (CDDP) (100 mg/sqm on day 1) and carmustine (BCNU) (160 mg/sqm on day 2); the treatment was repeated every 6 weeks for five cycles. Toxicity, progression free survival and overall survival were assessed.
Results
The median number of chemotherapy cycles delivered to each patient was 5 (range 3–6), with no patients discontinuing treatment because of refusal or toxicity. Dose reduction was required in 16 patients (10%), and all patients completed radiotherapy, whereas 5 patients discontinued chemotherapy before completing all planned cycles for disease progression. The primary toxicities were: neutropenia (grade 3–4: 23%), thrombocytopenia (grade 3–4: 18.5%), and nausea and vomiting (13%). Median progression-free survival times and 1-year progression free survival were 7.6 months (95% CI 6.6–8.5) and 17.3%, respectively. OS was 15.6 months (95% CI 14.1–17.1).
Conclusions
Our results for PFS and overall survival are comparable with those obtained with temozolomide, but the toxicity occurring in our series was more frequent and persistent. The toxicity, and mainly the modalities of administration associated with cisplatin and BCNU combination, argues against future use in the treatment of patients with GBM.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - mortality</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - radiotherapy</subject><subject>Carmustine - therapeutic use</subject><subject>Cisplatin - therapeutic use</subject><subject>Clinical Study-Patient Study</subject><subject>Combined Modality Therapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - mortality</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma - radiotherapy</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Oncology</subject><subject>Radiotherapy, Adjuvant</subject><subject>Retrospective Studies</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0167-594X</issn><issn>1573-7373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kMtKxDAUhoMozjj6AG6kuHBXPbk1zVKLNxh044C7kKbpTIfeTNrFvL0ZOjAguEog3__nnA-hawz3GEA8eIwhgRhAxjKFcDlBc8wFjQUV9BTNASci5pJ9z9CF91sAYILiczTDkmAigM3RU1b5vtZD1Y5NpNsieso-VpHZ2KYbNtbpfhdVbdS7qtFuF63rqstr7Yeu0VEfUrYd_CU6K3Xt7dXhXKDVy_NX9hYvP1_fs8dlbBjAELOSFVbrPE0LY3jKOHDBpC0IBZIwmRJNc1PSstRhKcELnCQap7mRCeGplIYu0N3U27vuZ7R-UE3lja1r3dpu9IoAIYIBCeDtH3Dbja4NsymCJZeYQBIgPEHGdd47W6rDkgqD2ttVk10V7Kq9XQUhc3MoHvPGFsfEQWcAyAT48NSurTv-_H_rL52lg7w</recordid><startdate>20090801</startdate><enddate>20090801</enddate><creator>Silvani, Antonio</creator><creator>Gaviani, Paola</creator><creator>Lamperti, Elena A.</creator><creator>Eoli, Marica</creator><creator>Falcone, Chiara</creator><creator>DiMeco, Francesco</creator><creator>Milanesi, Ida M.</creator><creator>Erbetta, Alessandra</creator><creator>Boiardi, Amerigo</creator><creator>Fariselli, Laura</creator><creator>Salmaggi, Andrea</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20090801</creationdate><title>Cisplatinum and BCNU chemotherapy in primary glioblastoma patients</title><author>Silvani, Antonio ; Gaviani, Paola ; Lamperti, Elena A. ; Eoli, Marica ; Falcone, Chiara ; DiMeco, Francesco ; Milanesi, Ida M. ; Erbetta, Alessandra ; Boiardi, Amerigo ; Fariselli, Laura ; Salmaggi, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-4f4deaab88dcc584505749ed230264982a3bcf3ffa10675d166a18bc9625899c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - radiotherapy</topic><topic>Carmustine - therapeutic use</topic><topic>Cisplatin - therapeutic use</topic><topic>Clinical Study-Patient Study</topic><topic>Combined Modality Therapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Glioblastoma - drug therapy</topic><topic>Glioblastoma - mortality</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma - radiotherapy</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Oncology</topic><topic>Radiotherapy, Adjuvant</topic><topic>Retrospective Studies</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Silvani, Antonio</creatorcontrib><creatorcontrib>Gaviani, Paola</creatorcontrib><creatorcontrib>Lamperti, Elena A.</creatorcontrib><creatorcontrib>Eoli, Marica</creatorcontrib><creatorcontrib>Falcone, Chiara</creatorcontrib><creatorcontrib>DiMeco, Francesco</creatorcontrib><creatorcontrib>Milanesi, Ida M.</creatorcontrib><creatorcontrib>Erbetta, Alessandra</creatorcontrib><creatorcontrib>Boiardi, Amerigo</creatorcontrib><creatorcontrib>Fariselli, Laura</creatorcontrib><creatorcontrib>Salmaggi, Andrea</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of neuro-oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Silvani, Antonio</au><au>Gaviani, Paola</au><au>Lamperti, Elena A.</au><au>Eoli, Marica</au><au>Falcone, Chiara</au><au>DiMeco, Francesco</au><au>Milanesi, Ida M.</au><au>Erbetta, Alessandra</au><au>Boiardi, Amerigo</au><au>Fariselli, Laura</au><au>Salmaggi, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cisplatinum and BCNU chemotherapy in primary glioblastoma patients</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2009-08-01</date><risdate>2009</risdate><volume>94</volume><issue>1</issue><spage>57</spage><epage>62</epage><pages>57-62</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><abstract>Background
The prognosis of patients with glioblastoma is very poor with a mean survival of 10–12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients. Methylated methylguanine methyltransferase (
MGMT
) promoter is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome
MGMT
-mediated chemoresistance are being actively investigated.
Methods
A retrospective analysis on 160 adult patients (≥16 years) treated for histologically confirmed GBM between 2003 and 2005 at our Institution was performed. All patients were treated with conventional fractionated radiotherapy and a combined chemotherapy treatment with Cisplatin (CDDP) (100 mg/sqm on day 1) and carmustine (BCNU) (160 mg/sqm on day 2); the treatment was repeated every 6 weeks for five cycles. Toxicity, progression free survival and overall survival were assessed.
Results
The median number of chemotherapy cycles delivered to each patient was 5 (range 3–6), with no patients discontinuing treatment because of refusal or toxicity. Dose reduction was required in 16 patients (10%), and all patients completed radiotherapy, whereas 5 patients discontinued chemotherapy before completing all planned cycles for disease progression. The primary toxicities were: neutropenia (grade 3–4: 23%), thrombocytopenia (grade 3–4: 18.5%), and nausea and vomiting (13%). Median progression-free survival times and 1-year progression free survival were 7.6 months (95% CI 6.6–8.5) and 17.3%, respectively. OS was 15.6 months (95% CI 14.1–17.1).
Conclusions
Our results for PFS and overall survival are comparable with those obtained with temozolomide, but the toxicity occurring in our series was more frequent and persistent. The toxicity, and mainly the modalities of administration associated with cisplatin and BCNU combination, argues against future use in the treatment of patients with GBM.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>19212704</pmid><doi>10.1007/s11060-009-9800-0</doi><tpages>6</tpages></addata></record> |
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| ispartof | Journal of neuro-oncology, 2009-08, Vol.94 (1), p.57-62 |
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| subjects | Adult Aged Antineoplastic Agents - therapeutic use Brain Neoplasms - drug therapy Brain Neoplasms - mortality Brain Neoplasms - pathology Brain Neoplasms - radiotherapy Carmustine - therapeutic use Cisplatin - therapeutic use Clinical Study-Patient Study Combined Modality Therapy Dose-Response Relationship, Drug Female Glioblastoma - drug therapy Glioblastoma - mortality Glioblastoma - pathology Glioblastoma - radiotherapy Humans Male Medicine Medicine & Public Health Middle Aged Neurology Oncology Radiotherapy, Adjuvant Retrospective Studies Survival Analysis Treatment Outcome Young Adult |
| title | Cisplatinum and BCNU chemotherapy in primary glioblastoma patients |
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