Literature DB >> 16983109

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03.

Ulrich Herrlinger1, Johannes Rieger, Dorothee Koch, Simon Loeser, Britta Blaschke, Rolf-Dieter Kortmann, Joachim P Steinbach, Thomas Hundsberger, Wolfgang Wick, Richard Meyermann, Ta-Chih Tan, Clemens Sommer, Michael Bamberg, Guido Reifenberger, Michael Weller.   

Abstract

PURPOSE: To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity.
RESULTS: A median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P = .014, log-rank test) and MST (P = .037).
CONCLUSION: The combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.

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Year:  2006        PMID: 16983109     DOI: 10.1200/JCO.2006.06.9104

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


  49 in total

1.  Imaging parameters of high grade gliomas in relation to the MGMT promoter methylation status: the CT, diffusion tensor imaging, and perfusion MR imaging.

Authors:  Won-Jin Moon; Jin Woo Choi; Hong Gee Roh; So Dug Lim; Young-Cho Koh
Journal:  Neuroradiology       Date:  2011-08-11       Impact factor: 2.804

Review 2.  MGMT promoter methylation in malignant gliomas.

Authors:  Markus J Riemenschneider; Monika E Hegi; Guido Reifenberger
Journal:  Target Oncol       Date:  2010-08-20       Impact factor: 4.493

3.  Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: a nested case-control study using the healthcore integrated research database.

Authors:  Vibha C A Desai; Scott C Quinlan; Anne C Deitz; Jinghua He; Crystal N Holick; Stephan Lanes
Journal:  J Neurooncol       Date:  2017-07-17       Impact factor: 4.130

4.  [Report from NeuroUpdate in Wiesbaden (13/14 February 2009)].

Authors:  M Dieterich; G F Hamann
Journal:  Nervenarzt       Date:  2009-06       Impact factor: 1.214

5.  [Lomustine and temozolomide in combination with radiotherapy : New treatment option for patients with MGMT promoter methylated Glioblastoma].

Authors:  Clemens Seidel; Rolf-Dieter Kortmann
Journal:  Strahlenther Onkol       Date:  2019-09       Impact factor: 3.621

6.  MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.

Authors:  Martin J van den Bent; Hendrikus J Dubbink; Marc Sanson; Cathleen R van der Lee-Haarloo; Monika Hegi; Judith W M Jeuken; Ahmed Ibdaih; Alba A Brandes; Martin J B Taphoorn; Marc Frenay; Denis Lacombe; Thierry Gorlia; Winand N M Dinjens; Johan M Kros
Journal:  J Clin Oncol       Date:  2009-11-09       Impact factor: 44.544

7.  Temozolomide: The evidence for its therapeutic efficacy in malignant astrocytomas.

Authors:  Ayman I Omar; Warren P Mason
Journal:  Core Evid       Date:  2010-06-15

Review 8.  Molecular diagnostics of gliomas: state of the art.

Authors:  Markus J Riemenschneider; Judith W M Jeuken; Pieter Wesseling; Guido Reifenberger
Journal:  Acta Neuropathol       Date:  2010-08-17       Impact factor: 17.088

Review 9.  Molecular neuropathology of gliomas.

Authors:  Markus J Riemenschneider; Guido Reifenberger
Journal:  Int J Mol Sci       Date:  2009-01-07       Impact factor: 6.208

10.  RNOP-09: pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study.

Authors:  Christoph P Beier; Christina Schmid; Thierry Gorlia; Christine Kleinletzenberger; Dagmar Beier; Oliver Grauer; Andreas Steinbrecher; Birgit Hirschmann; Alexander Brawanski; Christopher Dietmaier; Tanja Jauch-Worley; Oliver Kölbl; Torsten Pietsch; Martin Proescholdt; Petra Rümmele; Armin Muigg; Günther Stockhammer; Monika Hegi; Ulrich Bogdahn; Peter Hau
Journal:  BMC Cancer       Date:  2009-09-02       Impact factor: 4.430

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