Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma
This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma. The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada...
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| Veröffentlicht in: | Neurology 2011-09, Vol.77 (12), p.1156-1164 |
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| creator | WELLER, M GORLIA, T ROSSETTI, A. O LACOMBE, D MIRIMANOFF, R.-O VECHT, C. J STUPP, R CAIRNCROSS, J. G VAN DEN BENT, M. J MASON, W BELANGER, K BRANDES, A. A BOGDAHN, U MACDONALD, D. R FORSYTH, P |
| description | This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma.
The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors.
When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo. |
| doi_str_mv | 10.1212/WNL.0b013e31822f02e1 |
| format | Article |
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The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors.
When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.0b013e31822f02e1</identifier><identifier>PMID: 21880994</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic Agents, Alkylating - therapeutic use ; Biological and medical sciences ; Brain Neoplasms - drug therapy ; Brain Neoplasms - mortality ; Canada - epidemiology ; Dacarbazine - analogs & derivatives ; Dacarbazine - therapeutic use ; Europe - epidemiology ; Female ; Glioblastoma - drug therapy ; Glioblastoma - mortality ; Humans ; Male ; Medical sciences ; Middle Aged ; Neurology ; Neurosurgery ; Retrospective Studies ; Skull, brain, vascular surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Survival Rate - trends ; Valproic Acid - therapeutic use ; Young Adult</subject><ispartof>Neurology, 2011-09, Vol.77 (12), p.1156-1164</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 by AAN Enterprises, Inc. 2011 AAN Enterprises, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-c21fdae868305d88cd18bfaac5f5aca9e0f1dcc64585d9ffb6161586d3f80f793</citedby><cites>FETCH-LOGICAL-c520t-c21fdae868305d88cd18bfaac5f5aca9e0f1dcc64585d9ffb6161586d3f80f793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24587144$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21880994$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WELLER, M</creatorcontrib><creatorcontrib>GORLIA, T</creatorcontrib><creatorcontrib>ROSSETTI, A. O</creatorcontrib><creatorcontrib>LACOMBE, D</creatorcontrib><creatorcontrib>MIRIMANOFF, R.-O</creatorcontrib><creatorcontrib>VECHT, C. J</creatorcontrib><creatorcontrib>STUPP, R</creatorcontrib><creatorcontrib>CAIRNCROSS, J. G</creatorcontrib><creatorcontrib>VAN DEN BENT, M. J</creatorcontrib><creatorcontrib>MASON, W</creatorcontrib><creatorcontrib>BELANGER, K</creatorcontrib><creatorcontrib>BRANDES, A. A</creatorcontrib><creatorcontrib>BOGDAHN, U</creatorcontrib><creatorcontrib>MACDONALD, D. R</creatorcontrib><creatorcontrib>FORSYTH, P</creatorcontrib><title>Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma</title><title>Neurology</title><addtitle>Neurology</addtitle><description>This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma.
The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors.
When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - mortality</subject><subject>Canada - epidemiology</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - therapeutic use</subject><subject>Europe - epidemiology</subject><subject>Female</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - mortality</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neurosurgery</subject><subject>Retrospective Studies</subject><subject>Skull, brain, vascular surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Survival Rate - trends</subject><subject>Valproic Acid - therapeutic use</subject><subject>Young Adult</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUVtrFDEUDmKxa_UfiORFfJo2l8lM5kWQodXC0opU9C2cyWU3kpmsycxK_fWmdG3Vp3PgfLfDh9ArSk4po-zs69X6lAyEcsupZMwRZukTtKKCNVXD2benaEUIkxWXrTxGz3P-Tkg5tt0zdMyolKTr6hVSn1IMcdpYg_OS9n4PAf_08xaXZZei1xi0N3jJFvsJz1uLz68_3_RnV_1lj2c7xl-FPnpj8Zx84bqY8Cb4OATIcxzhBTpyELJ9eZgn6MvF-U3_sVpff7js368rLRiZK82oM2BlIzkRRkptqBwcgBZOgIbOEkeN1k0tpDCdc0NDGypkY7iTxLUdP0Hv7nV3yzBao-00Jwhql_wI6VZF8Orfy-S3ahP3irNGkLouAm8PAin-WGye1eiztiHAZOOSVUcYbzmjd1b1PVKnmHOy7sGFEnVXjSrVqP-rKbTXfyd8IP3pogDeHACQNQSXYNI-P-LK7y0tSX8DwLyayA</recordid><startdate>20110920</startdate><enddate>20110920</enddate><creator>WELLER, M</creator><creator>GORLIA, T</creator><creator>ROSSETTI, A. 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R</au><au>FORSYTH, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2011-09-20</date><risdate>2011</risdate><volume>77</volume><issue>12</issue><spage>1156</spage><epage>1164</epage><pages>1156-1164</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma.
The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors.
When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>21880994</pmid><doi>10.1212/WNL.0b013e31822f02e1</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Journals@Ovid Ovid Autoload; MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Antineoplastic Agents, Alkylating - therapeutic use Biological and medical sciences Brain Neoplasms - drug therapy Brain Neoplasms - mortality Canada - epidemiology Dacarbazine - analogs & derivatives Dacarbazine - therapeutic use Europe - epidemiology Female Glioblastoma - drug therapy Glioblastoma - mortality Humans Male Medical sciences Middle Aged Neurology Neurosurgery Retrospective Studies Skull, brain, vascular surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Survival Rate - trends Valproic Acid - therapeutic use Young Adult |
| title | Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma |
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