Document Detail


Chemoradiotherapy of newly diagnosed glioblastoma with intensified temozolomide.
MedLine Citation:
PMID:  19836157     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. PATIENTS AND METHODS: A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m(2) (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m(2)), maintenance TMZ starting at 150 mg/m(2) using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). RESULTS: The median follow-up interval was 21.7 months. Grade 4 hematologic toxicity was observed in 15 patients (36.6%). Treatment-related nonhematologic Grade 4-5 toxicity was reported for 2 patients (4.9%). The median progression-free survival was 7.6 months (95% confidence interval, 6.2-10.4). The 1-year survival rate was 73.2% (95% confidence interval, 56.8-84.2%). The presence of O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was associated with significantly superior progression-free survival. CONCLUSION: The dose-dense regimen of TMZ administered in a 1-week on/1-week off schedule resulted in acceptable nonhematologic toxicity. Compared with data from the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981-22981/CE.3, patients with an unmethylated MGMT gene promoter appeared not to benefit from intensifying the TMZ schedule regarding the median progression-free survival and overall survival. In contrast, data are promising for patients with a methylated MGMT promoter.
Authors:
Markus Weiler; Christian Hartmann; Dorothee Wiewrodt; Ulrich Herrlinger; Thierry Gorlia; Oliver B?hr; Richard Meyermann; Michael Bamberg; Marcos Tatagiba; Andreas von Deimling; Michael Weller; Wolfgang Wick
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study     Date:  2009-10-14
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  77     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-06-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  670-6     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of General Neurology, Hertie Institute for Clinical Brain Research, University of T?bingen, T?bingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Antineoplastic Agents, Alkylating / administration & dosage*,  adverse effects
Brain Neoplasms / drug therapy*,  enzymology,  mortality,  radiotherapy*
Combined Modality Therapy / methods
Confidence Intervals
DNA Methylation
DNA Modification Methylases / genetics
DNA Repair Enzymes / genetics
Dacarbazine / administration & dosage,  adverse effects,  analogs & derivatives*
Disease-Free Survival
Drug Administration Schedule
Female
Follow-Up Studies
Germany
Glioblastoma / drug therapy*,  enzymology,  mortality,  radiotherapy*
Humans
Indomethacin / administration & dosage
Karnofsky Performance Status
Male
Middle Aged
Prospective Studies
Survival Rate
Tumor Suppressor Proteins / genetics
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents, Alkylating; 0/Tumor Suppressor Proteins; 4342-03-4/Dacarbazine; 53-86-1/Indomethacin; 85622-93-1/temozolomide; EC 2.1.1.-/DNA Modification Methylases; EC 2.1.1.63/MGMT protein, human; EC 6.5.1.-/DNA Repair Enzymes

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