Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

Journal Article · Thu Jul 01 04:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.05.031· OSTI ID:21436022

Weiler, Markus ^[1]; Hartmann, Christian ^[2]; Wiewrodt, Dorothee ^[3]; Herrlinger, Ulrich ^[4]

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1. Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen (Germany)
2. Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg (Germany)
3. Department of Neurosurgery, University of Mainz, Mainz (Germany)
4. Clinical Neurooncology Unit, Department of Neurology, University of Bonn, Bonn (Germany)

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{sup 2} (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m{sup 2}), maintenance TMZ starting at 150 mg/m{sup 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{sup 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.

• OSTI ID: 21436022
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 77; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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