Article
Signifcance of COX-2, VEGF expression and microvessel density for antiangiogenic treatment of glioblastoma multiforme
Bedeutung der COX-II und VEGF-Expression sowie der Mikrogefäßdichte für einen antiangiogenen Therapieansatz bei Patienten mit Glioblastoma multiforme
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Published: | April 23, 2004 |
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Outline
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Objective
Glioblastoma multiforme (GBM) is the prototype of an angio-genic tumour. To evaluate the effects of an antiangiogenic treatment by a metronomic scheduling of Temozolomide (TMZ) and the COX-2 inhibitor Rofecoxib, expression of COX-2, VEGF and micro-vessel densitiy was evaluated and correlated with the therapeutic outcome.
Methods
Patients with GBM (n=13) were operated followed by radiotherapy and a continuous low dose therapy of 10 mg/m2 TMZ and 25 mg Rofecoxib/day. Tumour tissue was examined immunohistochemically for COX-2, VEGF and CD34 by monoclonal antibodies. Microvessel densitiy (MVD) was determined by morphometry. Mean follow-up was 14.4 ± 5.8 months. Therapy response was monitored by MR imaging and neurological examination.
Results
The mean time to progression of 10.6 ± 4.3 months in the response group was significantly higher compared to 3.8 ± 1.3 months in the non-responder group. The mean MVD was significantly higher in the responder group than in the non-responder group (5.43 ± 2.2% vs. 3.0 ± 1.5%). Tumours with a MVD <3.5% showed an earlier progress than tumours with a MVD >3.5%. Expression of COX-2 was higher in tumours with a high MVD than in tumours with a low MVD. Also, COX-2 showed a significantly stronger expression in responders than in non-responders. VEGF also exhibited a stronger expression in tumours with a high MVD.
Conclusions
Adjuvant metronomic chemotherapy with TMZ and Rofecoxib shows a promising effect in highly vascularized glioblastomas. Expression of COX-2, VEGF and MVD seem to be important factors in predicting a successful antiangiogenic adjuvant treatment.