Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

Oct 20, 2009International journal of radiation oncology, biology, physics

Chemoradiotherapy with increased temozolomide in newly diagnosed glioblastoma

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Abstract

The median progression-free survival was 7.6 months in 41 patients treated with a dose-dense regimen of temozolomide.

Grade 4 hematologic toxicity occurred in 15 patients (36.6%), while nonhematologic Grade 4-5 toxicity was observed in 2 patients (4.9%).
The 1-year survival rate for patients was 73.2% (95% confidence interval, 56.8-84.2%).
Tumors with O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation showed significantly better progression-free survival.
Patients with an unmethylated MGMT gene promoter did not show benefit from the intensified temozolomide schedule in terms of median progression-free survival and overall survival.

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

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Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide

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