Chemoradiotherapy of newly diagnosed glioblastoma with intensified temozolomide.

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. 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). 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. 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.

Weiler M ，Hartmann C ，Wiewrodt D ，Herrlinger U ，Gorlia T ，Bähr O ，Meyermann R ，Bamberg M ，Tatagiba M ，von Deimling A ，Weller M ，Wick W ... -  《-》

MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.

Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m(2) per day)/one week off] or Arm B [3 weeks on (80 mg/m(2) per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8-3.2 vs. B: 2.0 months; 95% CI, 1.8-3.5] and overall survival [A: 9.8 months (95% CI, 6.7-13.0) vs. B: 10.6 months (95% CI, 8.1-11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8-7.4) versus 1.8 months (95% CI, 1.8-2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation.

Weller M ，Tabatabai G ，Kästner B ，Felsberg J ，Steinbach JP ，Wick A ，Schnell O ，Hau P ，Herrlinger U ，Sabel MC ，Wirsching HG ，Ketter R ，Bähr O ，Platten M ，Tonn JC ，Schlegel U ，Marosi C ，Goldbrunner R ，Stupp R ，Homicsko K ，Pichler J ，Nikkhah G ，Meixensberger J ，Vajkoczy P ，Kollias S ，Hüsing J ，Reifenberger G ，Wick W ，DIRECTOR Study Group ... -  《-》

Long-term therapy with temozolomide is a feasible option for newly diagnosed glioblastoma: a single-institution experience with as many as 101 temozolomide cycles.

Barbagallo GM ，Paratore S ，Caltabiano R ，Palmucci S ，Parra HS ，Privitera G ，Motta F ，Lanzafame S ，Scaglione G ，Longo A ，Albanese V ，Certo F ... -  《Neurosurgical Focus》

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study.

Lombardi G ，Rumiato E ，Bertorelle R ，Saggioro D ，Farina P ，Della Puppa A ，Zustovich F ，Berti F ，Sacchetto V ，Marcato R ，Amadori A ，Zagonel V ... -  《-》

MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.

Brandes AA ，Franceschi E ，Tosoni A ，Blatt V ，Pession A ，Tallini G ，Bertorelle R ，Bartolini S ，Calbucci F ，Andreoli A ，Frezza G ，Leonardi M ，Spagnolli F ，Ermani M ... -  《-》