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
Current and future developments in the use of temozolomide for the treatment of brain tumours
TL;DR: The pharmacological background and clinical development of temozolomide is summarized and current and future clinical exploration of this drug for the treatment of brain tumours are focused on.
Journal ArticleDOI
In vitro evaluation of temozolomide combined with X-irradiation
TL;DR: The combination of temozolomide with radiation is at best additive, but could nonetheless be of considerable therapeutic benefit in glioma, particularly if administered for prolonged periods.
Journal ArticleDOI
Survival of human glioma cells treated with various combination of temozolomide and X-rays.
TL;DR: Depending on the cell line, treatment of glioma cells with temozolomide and X-rays can have either an additional effect or potentiate cell killing.
Journal ArticleDOI
Single-Arm, Open-Label Phase II Study of Intravenously Administered Tirapazamine and Radiation Therapy for Glioblastoma Multiforme
J. Del Rowe,Charles B. Scott,Maria Werner-Wasik,Jean-Paul Bahary,Walter J. Curran,Raul C. Urtasun,Barbara Fisher +6 more
TL;DR: Survival in the population treated with radiation and tirapazamine was equivalent to the control population, and patients in RPA class III treated with Radiation Therapy Oncology Group (RTOG) patients with glioblastoma multiforme patients had a longer survival when compared with the historical controls.
Journal ArticleDOI
Chemotherapy for high-grade gliomas.
Evanthia Galanis,Jan C. Buckner +1 more
TL;DR: High response rates achieved with agents that do not easily cross the blood–brain barrier, such as cisplatin in patients chemosensitive central nervous system (CNS) tumours, embryonal tumours of the CNS and germ tumours underscore the importance of chemoresponsiveness rather than blood– brain bar being a major determinant of brain tumour response chemotherapy.
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Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.
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