Bevacizumab, temozolomide, and radiation therapy followed by bevacizumab, temozolomide, and oral topotecan for newly-diagnosed glioblastoma multiforme (GBM).

2098 Background: The prognosis for newly-diagnosed GBM remains poor. Adding temozolomide to radiation therapy improved the median event-free survival (EFS) to 6.9 months and median overall survival to 14.6 months. The five year survival remains < 10%. GBM's have abundant neo-vascularization and the highest level of vascular endothelial growth factor (VEGF). Bevacizumab is an antibody to VEGF and is the most active agent for recurrent GBM. Hypoxia inducing factor-1 α (HIF-1 α) is an important regulator of VEGF, and topotecan may inhibit HIF-1 α. We performed a phase II trial in newly diagnosed GBM patients, adding bevacizumab and topotecan to standard therapy. METHODS: Eighty newly diagnosed GBM patients were enrolled after their craniotomy between December 2009 and December 2010. Patients received standard radiation therapy and temozolomide at 75 mg/m(2)/d beginning between 2-6 weeks post-craniotomy. Bevacizumab, 10 mg/kg every 14 days was added a minimum of 4 weeks post-op. Two weeks after radiation therapy was completed, 12 monthly cycles of temozolomide at 150-200 mg/m(2)/d days 1-5, oral topotecan at 1.5 mg/m(2/)day days 2-6 for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 2.0 mg/m(2)/day days 2-6 for patients on an EIAED bevacizumab at 10 mg/kg on days 1 and 15. RESULTS: Adding bevacizumab and topotecan to standard therapy resulted in a 6-month EFS of 90%. The median overall survival has not been reached, but 96% of the patients are alive at 8 months. The regimen was tolerable, 96% completed radiation therapy. Eight patients came off due to toxicity, there were 2 CNS hemorrhages, 2 grade 4 thrombocytopenias, 1 pulmonary embolus, 1 colon perforation, 1 craniotomy bone flap infection, and 1 CMV pneumonitis. There were 2 toxic deaths, 1 from CMV pneumonits and 1 from CNS hemorrhage. There are 10 progressions. A comprehensive analysis of tumor biomarkers is underway. CONCLUSIONS: Adding bevacizumab to temozolomide and radiation followed by temozolomide, bevacizumab and oral topotecan is tolerable. The 6-month EFS is encouraging. Randomized phase III trials of the addition of bevacizumab to the treatments of newly diagnosed GBM patients are essential.

Duke Scholars

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology