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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, K; Kirkpatrick, J; Coan, AD; Bailey, L; Janney, D; Lu, C; Friedman, HS

Published Date

  • May 20, 2011

Published In

Volume / Issue

  • 29 / 15_suppl

Start / End Page

  • 2098 -

PubMed ID

  • 28019863

Pubmed Central ID

  • 28019863

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Language

  • eng

Conference Location

  • United States