gms | German Medical Science

Background: Glioblastoma multiforme is the prototype of an angiogenic tumor and thus predestined for an antiangiogenic therapy. Due to the lack of clinically available antiangiogenic drugs continuous low dose chemotherapy in combination with a COX-II inhibitor was investigated as an antiangiogenic approach in patients with glioblastoma multiforme. The aim of this study was to evaluate the safety, feasibility and biological activity of a continuous low dose application of temozolomide and rofecoxib/celecoxib.

Methods: 30 Patients with primary glioblastoma multiforme received after operation and radiation therapy continuous low dose chemotherapy with temozolomide (up to 20mg/m2) and the COX-II Inhibitor rofecoxib (25md/day) or celecoxib (200mg/day). Clinical and MRI follow up examination was done every 8 weeks. Tumor tissue was analysed for microvessel density, COX-II expression and VEGF expression in 13 patients.

Results: Mean follow up time was 20 months. Mean progression free survival of all patients was 9.6 months; mean overall survival was 17.0 months. Patients with a higher micro-vessel density responded significantly better to the therapy (PFS 11.7 vs. 6.7 months). 16 out of 30 Patients (53%) suffered a tumor recurrence distant to the original tumor-localisation. These patients had a slightly shorter overall survival. There was no relationship of the immunhistochemical markers and the incidence of distant tumor recurrence.

Conclusion: Continuous low dose chemotherapy with temozolomide and a COX-II inhibitor seems to be a safe, feasible and biological active therapy option in highly vascularized tumors. Despite the increase in distant tumor recurrences compared to historical controls the continuos low dose chemotherapy seems to be a promising therapy option since the progression free survival and the overall survival compare very well to actual studies.