Weller, Michael and Tabatabai, Ghazaleh and Kaestner, Baerbel and Felsberg, Joerg and Steinbach, Joachim P. and Wick, Antje and Schnell, Oliver and Hau, Peter and Herrlinger, Ulrich and Sabel, Michael C. and Wirsching, Hans-Georg and Ketter, Ralf and Baehr, Oliver and Platten, Michael and Tonn, Joerg C. and Schlegel, Uwe and Marosi, Christine and Goldbrunner, Roland and Stupp, Roger and Homicsko, Krisztian and Pichler, Josef and Nikkhah, Guido and Meixensberger, Juergen and Vajkoczy, Peter and Kollias, Spyros and Huesing, Johannes and Reifenberger, Guido and Wick, Wolfgang (2015) MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial. CLINICAL CANCER RESEARCH, 21 (9). pp. 2057-2064. ISSN 1078-0432, 1557-3265
Full text not available from this repository. (Request a copy)Abstract
Purpose: 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. Experimental Design: 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. Results: 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, 1.87.4) 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. Conclusions: 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. (C) 2015 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEWLY-DIAGNOSED GLIOBLASTOMA; PHASE-II TRIAL; SINGLE-AGENT BEVACIZUMAB; HIGH-GRADE GLIOMA; RECURRENT GLIOBLASTOMA; MALIGNANT GLIOMA; RANDOMIZED-TRIAL; CLINICAL-TRIAL; LOMUSTINE; RADIOTHERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2019 06:08 |
| Last Modified: | 22 Jul 2019 06:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5588 |
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