Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

Weiler, Markus; Hartmann, Christian; Wiewrodt, Dorothee; Herrlinger, Ulrich; Gorlia, Thierry; Bähr, Oliver; Meyermann, Richard; Bamberg, Michael; Tatagiba, Marcos; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang

doi:10.1016/j.ijrobp.2009.05.031

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 77, Issue 3 , Pages 670-676, 1 July 2010

Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

Presented orally at the Eighth Meeting of the European Association of Neuro-Oncology, September 12–14, 2008, Barcelona, Spain.

Markus Weiler, M.D.
- Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Department of Neurooncology, University of Heidelberg, Heidelberg, Germany
Christian Hartmann, M.D.
- Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany
Dorothee Wiewrodt, M.D.
- Department of Neurosurgery, University of Mainz, Mainz, Germany
Ulrich Herrlinger, M.D.
- Clinical Neurooncology Unit, Department of Neurology, University of Bonn, Bonn, Germany
Thierry Gorlia, M.Sc.
- European Organization for Research and Treatment of Cancer Data Centre, Brussels, Belgium
Oliver Bähr, M.D.
- Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Richard Meyermann, M.D.
- Department of Neuropathology, University of Tübingen, Tübingen, Germany
Michael Bamberg, M.D.
- Department of Radiation Oncology, University of Tübingen, Tübingen, Germany
Marcos Tatagiba, M.D.
- Department of Neurosurgery, University of Tübingen, Tübingen, Germany
Andreas von Deimling, M.D.
- Department of Neuropathology, University of Heidelberg, Heidelberg, Germany
Michael Weller, M.D.
- Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Department of Neurology, University Hospital of Zurich, Zurich, Switzerland
Wolfgang Wick, M.D.
- Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- Department of Neurooncology, University of Heidelberg, Heidelberg, Germany
- Reprint requests to: Wolfgang Wick, M.D., Department of Neurooncology, University of Heidelberg, Im Neuenheimer Feld 400, Heidelberg D-69120 Germany. Tel: (+49) 6221-56-7075; Fax: (+49) 6221-56-7554

Received 23 February 2009; received in revised form 24 May 2009; accepted 26 May 2009. published online 15 October 2009.

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/m² (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m²), maintenance TMZ starting at 150 mg/m² 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 O⁶-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.

Glioblastoma, indomethacin, O⁶-methylguanine-DNA methyltransferase, MGMT, radiotherapy, temozolomide