Use of Anti-angiogenic Agents in Glioblastoma Treatment
Abstract & Commentary
By Adília Hormigo, MD, PhD, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Hormigo reports no financial relationships relevant to this field of study.
Synopsis: The anti-angiogenic monoclonal antibody, bevacizumab, shows great promise in the treatment of malignant gliomas.
Source: Ali SA, McHayleh WM, Ahmad A, et al. Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases. J Neurosurg 2008;109:268-272.
Glioblastoma (GBM) is one of the most common of the primary brain tumors and has a median survival of 12-14 months. At recurrence, the median survival is 3-6 months, with less than 10% having a progression-free survival of 6 months.
In this study, the authors used bevacizumab plus irinotecan to treat 13 patients with GBM who had failed initial standard treatment of resection followed by radiotherapy with concurrent chemotherapy or who had tumor progression or recurrent disease after multiple treatment regimens. They treated 9 patients with bevacizumab at a dose of 5 mg/m2 every 2 weeks and irinotecan at a dose of 125 mg/m2 every week for 3 weeks followed by one week off. Four patients were treated with bevacizumab 10 mg/m2 with irinotecan at 125-250 mg/m2 every 2 weeks. Six patients (46%) had a clinical response. By imaging criteria, 10 patients (77%) had a partial response, defined as >50% reduction in edema and enhancement, along with a 25% reduction in total tumor mass. Three patients (23%) had stable disease. Median time to progression was 24 weeks and median overall survival was 27 weeks. The authors reported nonfatal intracranial hemorrhage in two patients and deep venous thrombosis in another.
Commentary
The results of this observational study support prior data that showed benefit of bevacizumab in combination with irinotecan or other agents for treatment of patients with GBM and recurrent disease. This suggests that bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, is the key drug in these regimens and supports further trials using anti-angiogenic compounds in the treatment of GBM. The drug is generally well tolerated and the studies reveal a positive effect on survival. Potential serious complications are intracerebral hemorrhage and stroke, and over time some patients may develop hypertension and proteinuria with renal dysfunction. The MRI responses were remarkable, with rapid reduction in tumor mass in the responders. However, in patients on bevacizumab who have a clinical deterioration and increased hyperintensity on FLAIR (fluid attenuation inversion recovery) but a sustained reduction in contrast-enhancement on MRI, the MRI has to be interpreted with caution since it can be difficult to determine if this represents tumor growth or tissue necrosis. MRI has limitations in evaluating therapeutic response to biological agents. In some of the cases, non-enhancing tumor developed rapidly and raises the question of whether bevacizumab has a role in the development of more aggressive tumor. The results of future trials will determine whether anti-angiogenic agents should be administered concurrently with the standard treatment of radiotherapy combined with chemotherapy.
References
1. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-4729.
2. Pope WB, Lai A, Nghiemphu P, et al. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology 2006;66:1258-1260.
The anti-angiogenic monoclonal antibody, bevacizumab, shows great promise in the treatment of malignant gliomas.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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