Combined regimen of temozolomide and liposomal pegylated doxorubicin in glioblastoma--Toxicity and Efficacy.

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Abstract No:

11501

Citation:

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 11501

Author(s):

U. Bogdahn, T. Jauch, C. Beier, D. Beier, S. Gänßbauer, M. Glas, H. Koch, C. Wismeth, A. Steinbrecher, P. Hau

Abstract:

Background: Temozolomide (Temodar, TMZ) recently showed promising efficacy in an EORTC trial on first-line therapy of glioblastoma (Stupp R, 2005). Pegylated liposomal doxorubicin (Caelyx, PEG-DOX) was evaluated in patients with recurrent high-grade glioma and showed an overall response rate of 40% (Hau P, 2002). Therefore, a combination of both agents seems promising. Methods: TMZ was given orally 75 mg/m² daily during standard radiotherapy (initiation) and 150-200 mg/m2 days 1-5 in 28 days starting 4 weeks after radiotherapy (maintainance). PEG-DOX was given as a short-time infusion in a dose-escalation regimen once prior to radiotherapy and on days 1 and 15 starting 4 weeks after radiotherapy. PEG-DOX was escalated for 5 mg/m² in groups of three patients starting with 5 mg/m² (group 1) and a highest dose of 20 mg/m² (group 4). Results: In the dose escalation part of this study, the regime detailed above was feasible, tolerable, and able to induce objective responses and stabilizations in patients with glioblastoma. In the first treatment group (5 mg/m² of PEG-Dox), one out of 7 evaluable patients had a dose limiting toxicity (DLT). In the second, third and fourth treatment groups, the regimen was tolerated without DLT. Concerning efficacy in the "treated-patients" analysis of 18 patients, 1 had a partial response in MRI, and 12 patients had tumor stabilization 4 weeks after conclusion of radiotherapy. Only 5 patients progressed early. Twelve patients responded with progression free survival times of 13 to 76 weeks. One patient is still progression free after 120 weeks of treatment. Conclusion: As no DLT was observed in dose group 4, MTD was not reached and we proceed to the efficacy phase of the trial with PEG-DOX in a dose of 20 mg/m². Seventeen patients are included so far. Results will be compared to the published study EORTC 26981/22981 (Stupp R et al., 2005) which did set a new standard in the first-line treatment of glioblastoma as survival times of more than 14 months and a 2-year overall survival of 26% were reached. Regarding the promising preliminary survival data of study RNOP-09, we expect even better results with the regimen used in this protocol.