Journal ArticleDOI
Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide
Roger Stupp,Pierre Yves Dietrich,Sandrine Ostermann Kraljevic,Alessia Pica,Ivan Maillard,Phillipe Maeder,Reto Meuli,Robert C. Janzer,Gianpaolo Pizzolato,Raymond Miralbell,F. Porchet,Luca Regli,Nicolas de Tribolet,René O. Mirimanoff,Serge Leyvraz +14 more
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TLDR
This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma.Abstract:
PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m2/d × 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy × 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m2/d × 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During t...read more
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Journal ArticleDOI
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Roger Stupp,Warren P. Mason,Martin J. van den Bent,Michael Weller,Barbara Fisher,Martin J.B. Taphoorn,Karl Belanger,Alba A. Brandes,Christine Marosi,Ulrich Bogdahn,Jürgen Curschmann,Robert C. Janzer,Samuel K. Ludwin,Thierry Gorlia,Anouk Allgeier,Denis Lacombe,J. Gregory Cairncross,Elizabeth Eisenhauer,René O. Mirimanoff +18 more
TL;DR: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Journal ArticleDOI
Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
Roger Stupp,Monika E. Hegi,Warren P. Mason,Martin J. van den Bent,Martin J.B. Taphoorn,Robert C. Janzer,Samuel K. Ludwin,Anouk Allgeier,Barbara Fisher,Karl Belanger,Peter Hau,Alba A. Brandes,J.M.M. Gijtenbeek,Christine Marosi,Charles J. Vecht,Karima Mokhtari,Pieter Wesseling,Salvador Villà,Elizabeth Eisenhauer,Thierry Gorlia,Michael Weller,Denis Lacombe,J. Gregory Cairncross,René-Olivier Mirimanoff +23 more
TL;DR: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up, and a benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
Journal ArticleDOI
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Journal ArticleDOI
Boron neutron capture therapy of cancer: current status and future prospects.
TL;DR: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor borons content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy.
Journal ArticleDOI
Clinical Trial Substantiates the Predictive Value of O-6-Methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastoma Patients Treated with Temozolomide
Monika E. Hegi,Annie Claire Diserens,Sophie Godard,Pierre-Yves Dietrich,Luca Regli,Sandrine Ostermann,Philippe Otten,Guy van Melle,Nicolas de Tribolet,Nicolas de Tribolet,Roger Stupp +10 more
TL;DR: The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.
References
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Journal ArticleDOI
Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
Michael Brada,Khê Hoang-Xuan,R. Rampling,Pierre Yves Dietrich,Luc Dirix,David R. Macdonald,J. J. Heimans,B. A. Zonnenberg,Jose Bravo-Marques,Roger Henriksson,Roger Stupp,N. Yue,Janet M. Bruner,M. Dugan,S. Rao,Sara L. Zaknoen +15 more
TL;DR: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM, and should be explored further in an adjuvant setting and in combination with other agents.
Journal Article
p53 Effects Both the Duration of G2/M Arrest and the Fate of Temozolomide-treated Human Glioblastoma Cells
TL;DR: The results suggest that glioma cells respond to TMZ by undergoing G2-M arrest, and the integrity of the G1-M cell cycle checkpoint may be important in the cytotoxicity of TMZ in gliomas.
Journal ArticleDOI
Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06
Charles Scott,Charles W. Scarantino,Raul Urtasun,Benjamin Movsas,Christopher U Jones,Joseph R Simpson,A. Jennifer Fischbach,Walter J. Curran +7 more
TL;DR: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival, and their usefulness as historical controls for the comparison of future Phase II results is attested.
Journal Article
Phase I Trial of Temozolomide Using an Extended Continuous Oral Schedule
Cathryn S Brock,Edward S. Newlands,Steven R. Wedge,Mark Bower,Helen H. Evans,Iain Colquhoun,Mary Roddie,M.G. Glaser,Maureen H. Brampton,Gordon J. S. Rustin +9 more
TL;DR: Toxicity was greatest in higher dose cohorts, with a resultant maximum tolerated dose of 85 mg/m2/day, whereas lower dose cohorts tolerated the schedule well, and the area under the temozolomide plasma versus time curve was noncumulative between the first and last week of the schedule.
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Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
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Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
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