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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses the results of the multicenter, randomized, open-label, controlled, Phase 3 Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status study [CENTRIC; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00689221\u0026amp;atom=%2Fspmdc%2F13%2F6%2F15.atom\u0022\u003ENCT00689221\u003C\/a\u003E; \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr LBA2009)].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERadiation Therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHead \u0026amp; Neck Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERadiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERadiation Therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHead \u0026amp; Neck Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERadiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ERoger Stupp, MD, University of Zurich, Zurich, Switzerland, discussed the results of the multicenter, randomized, open-label, controlled, Phase 3 Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status study [CENTRIC; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00689221\u0026amp;atom=%2Fspmdc%2F13%2F6%2F15.atom\u0022\u003ENCT00689221\u003C\/a\u003E; \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013 (suppl; abstr LBA2009)].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ECilengitide (CIL) is a cyclic arginine, glycine, and aspartic acid-containing pentapeptide that inhibits \u03b1v\u00df3 and \u03b1v\u00df5 integrins, which are expressed on glioblastoma cells. The CENTRIC study explored the use of CIL combined with standard treatment comprising temozolomide (TMZ) and radiation therapy (RT) for patients with newly diagnosed glioblastoma and methylated \u003Cem\u003EO-6 Methylguanine-DNA Methyltransferase (MGMT)\u003C\/em\u003E gene promoter. Prior Phase 2 trials had suggested a benefits of CIL doses of 500 and 2000 mg on overall survival (OS) and progression-free survival (PFS), with superior outcome of higher versus lower dosage of CIL (2000 vs 500 mg) and little added toxicity [Reardon DA et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008; Nabors LB et al. \u003Cem\u003ECancer\u003C\/em\u003E 2012]. In comparison with historical controls the enhanced benefits of the combination of CIL added to standard TMZ\/RT\u279dTMZ concomitant and adjuvant TMZ and RT treatment sequence was particularly pronounced in tumors containing a \u003Cem\u003EMGMT\u003C\/em\u003E gene promoter methylation [Stupp R et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThis pivotal Phase 3 trial was conducted at over 200 sites worldwide. Eligibility criteria for the 545 patients were aged \u226518 years, newly diagnosed and histologically proven glioblastoma, methylated \u003Cem\u003EMGMT\u003C\/em\u003E promoter, ECOG PS 0 to 1, and stable or decreasing use of steroids. A total of 545 patients were randomized to standard treatment [Stupp R et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2005] with TMZ\/RT\u279dTMZ and CIL (2000 mg IV BIW) or standard therapy alone. Maintenance TMZ was given for up to 6 cycles, CIL was to be given until disease progression up to 2 years.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary endpoint was OS, secondary endpoints were PFS, safety and tolerability, QT\/QTc elevation, population pharmacokinetics, general health and work status, and quality of life. The median follow-up was 29 months.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EBaseline characteristics in the intention-to-treat population were similar in terms of median age, male sex, ECOG PS, extent of surgery, recursive portioning analysis class, median weeks to randomization, and use of steroid and seizure medications.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThis study failed to meet the primary endpoint as no differences in OS were evident (median treatment OS, 26.3 months; 95% CI, 23.8 to 28.8; median control OS, 26.3 months; 95% CI, 23.9 to 34.7; HR, 1.021; 95% CI, 0.808 to 1.291; p=0.8623; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Further analyses of the patients according to parameters including age, ethnicity, region of origin, and extent of surgery did not reveal any significance in terms of OS. Similarly, no differences between the patient groups were apparent for PFS as determined by the individual investigators (median treatment PFS, 13.5 months; 95% CI, 10.8 to 15.9; median control PFS, 10.7 months; 95% CI, 8.1 to 13.3; HR, 0.926; 95% CI, 0.757 to 1.133; p=0.4570) and an overall determination by independent assessors (median treatment OS, 10.6 months; 95% CI, 8.2 to 13.4; median control PFS, 7.9 months; 95% CI, 5.9 to 12.5; HR, 0.918; 95% CI, 0.750 to 1.124; p=0.4102).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EToxicity in both arms was mainly related to TMZ and RT. The marginally increased incidence of pulmonary embolism in the CIL-treated patients (12 vs 5 patients) was not considered clinically relevant. Other adverse events in the two study arms were similar in the two treatment arms.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/15\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Overall Survival: Intent to Treat\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1025193158\u0022 data-figure-caption=\u0022Overall Survival: Intent to Treat\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/15\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/15\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/15\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13445\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EOverall Survival: Intent to Treat\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from R Stupp, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EThe researchers concluded that CIL applied with the standard therapeutic combination of TMZ and RT did not prolong survival, with no patient subgroup exhibiting a clinical benefit. No new safety concerns were evident.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/6\/15.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznvn2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznvn2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}