Phase I/II study of cetuximab plus temozolomide as radiochemotherapy for primary glioblastoma (GERT)
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Posted on: 10/04/2008
Phase I/II study of cetuximab plus temozolomide as radiochemotherapy for primary glioblastoma (GERT)--Eudract number 2005-003911-63; NCT00311857.
Central Nervous System Tumors
Central Nervous System Tumors
2008 ASCO Annual Meeting
J Clin Oncol 26: 2008 (May 20 suppl; abstr 2077)
S. E. Combs, D. Schulz-Ertner, C. Hartmann, T. Welzel, C. Timke, K. Herfarth, A. von Deimling, L. Edler, M. Platten, W. Wick, J. Debus
Background: Glioblastomas (GB) are known to express high levels of EGFR; targeting of EGFR using cetuximab has proven to be a successful treatment. This phase I/II trial of radiochemotherapy (RCHT) with TMZ and cetuximab in patients with primary GB evaluates feasibility and toxicity. Methods: Seventeen patients with pathologically confirmed GB were included into this analysis. Radiotherapy (RT) is delivered with a median dose of 60 Gy, 5*2Gy/week. TMZ is prescribed concomitantly at a dose of 75mg/m2, followed by 6 cycles of adjuvant TMZ. Cetuximab is applied as weekly infusions (loading dose 400 mg/m2 on day 1, and concomitant with RT on days 8, 15, 22, 29, 36, 43 at 250 mg/m2). Fourteen patients were male and 3 patients were female. Median age at diagnosis was 48 years. Neurosurgical resections had been complete in 7, subtotal in 7, and a biopsy in 3 patients. O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation was investigated in the tumor tissue: 33% of the patients were MGMT-positive, and 66% were MGMT-negative. EGFR-analysis is currently being conducted. Treatment was initiated after a median of 15 days after primary diagnosis. Median follow-up time at the time of this analysis was 13 months. Results: RCHT with cetuximab is safe and well tolerated. Cetuximab-related side effects included acneiform rash. In one patient cetuximab infusions were discontinued after occurrence of bilateral pulmonary embolism in treatment week 7. One patient died in treatment week 4 after tumor progression and massive brain edema which could not be controlled by medication including high-dose steroids. In all other patients the scheduled 7 cycles of cetuximab could be applied. Overall survival (OS) was 87% at 12 months. No prognostic factors could be determined until now. Methylated MGMT was not associated with longer OS (p=0.22). Progression-free survival (PFS) was 81% at 6 months and 37% at 12 months. Methylated MGMT was not associated with longer PFS (p=0.59). No prognostic factors of PFS could be identified. Conclusions: Early data from trimodal therapy in GB patients with RT, TMZ and cetuximab indicate feasibility without an increased toxicity profile. PFS as well as OS appear to be very promising.
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