Bogdahn, Ulrich and Hau, P. and Stockhammer, G. and Venkataramana, N. K. and Mahapatra, A. K. and Suri, A. and Balasubramaniam, A. and Nair, S. and Oliushine, V. and Parfenov, V. and Poverennova, I. and Zaaroor, M. and Jachimczak, P. and Ludwig, S. and Schmaus, S. and Heinrichs, H. and Schlingensiepen, K-H (2011) Targeted therapy for high-grade glioma with the TGF-beta 2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. NEURO-ONCOLOGY, 13 (1). pp. 132-142. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)Abstract
This randomized, open-label, active-controlled, dose-finding phase fib study evaluated the efficacy and safety of trabedersen (AP 12009) administered intratumorally by convection-enhanced delivery compared with standard chemotherapy in patients with recurrent/refractory high-grade glioma. One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) were randomly assigned to receive trabedersen at doses of 10 or 80 mu M or standard chemotherapy (temozolomide or procarbazine/lomustine/ vincristine). Primary endpoint was 6-month tumor control rate, and secondary endpoints included response at further timepoints, survival, and safety. Six-month tumor control rates were not significantly different in the entire study population (AA and GBM). Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 mu M trabedersen vs chemotherapy (p=.0032). The 2-year survival rate had a trend for superiority for 10 mu M trabedersen vs chemotherapy (p=.10). Median survival for 10 mu M trabedersen was 39.1 months compared with 35.2 months for 80 mu M trabedersen and 21.7 months for chemotherapy (not significant). In GBM patients, response and survival results were comparable among the 3 arms. Exploratory analysis on GBM patients aged <= 55 years with Karnofsky performance status >80% at baseline indicated a 3-fold survival at 2 and 3 years for 10 mu M trabedersen vs chemotherapy. The frequency of patients with related or possibly drug-related adverse events was higher with standard chemotherapy (64%) than with 80 mu M trabedersen (43%) and 10 mu M trabedersen (27%). Superior efficacy and safety for 10 mu M trabedersen over 80 mu M trabedersen and chemotherapy and positive risk-benefit assessment suggest it as the optimal dose for further clinical development in high-grade glioma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECURRENT MALIGNANT GLIOMA; GROWTH-FACTOR BETA-2; PROGNOSTIC-FACTORS; BRAIN-TUMORS; ADJUVANT TEMOZOLOMIDE; CLINICAL-TRIALS; TGF-BETA; GLIOBLASTOMA; IMMUNOSUPPRESSION; CONCOMITANT; anaplastic astrocytoma; antisense oligonucleotide; convection-enhanced delivery; glioblastoma multiforme; recurrent or refractory high-grade glioma; targeted therapy; temozolomide; trabedersen; transforming growth factor beta 2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Jul 2020 08:36 |
| Last Modified: | 01 Jul 2020 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21635 |
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