Bevacizumab and irinotecan for recurrent oligodendroglial tumors
Marc C.Chamberlain, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, SCCA, 825 Eastlake Ave East, PO Box 19023, MS G4940, Seattle, WA 98109chambemc@u.washington.edu
Submitted July 31, 2009
We commend Tallibert et al. for their article regarding the efficacy of bevacizumab and irinotecan for recurrent oligodendroglial tumors. [1]
Bevacizumab was recently approved for treatment of recurrent glioblastoma by the US Food and Drug Administration. It was approved as a single agent because there is no data showing a survival benefit in combining it with irinotecan. Furthermore, irinotecan adds both cost and toxicity. These issues are relevant to the retrospective study by Tallibert al. because data regarding the added benefit of combining irinotecan with bevacizumab for recurrent anaplastic gliomas (AG) is equally uncertain.
We investigated the use of single agent bevacizumab for both recurrent anaplastic astrocytoma and anaplastic co-deleted oligodendrogliomas and saw similar outcomes with respect to overall response rate, mPFS, and 6-month progression free survival. [2, 3] Our data, similar to that for recurrent glioblastoma, do not indicate any value in adding irinotecan to bevacizumab for recurrent AG. A prospective trial of bevacizumab with or without irinotecan for recurrent AG is needed to adjudicate this issue.
Tallibert et al. treated seven patients with World Health Organization grade 2 tumors that appeared to have dedifferentiated by neuroradiology into grade 3 tumors. Whether transformation into a higher grade can be determined by anatomic MR imaging is debatable. In addition, whether low grade gliomas respond to bevacizumab is uncertain although available data suggests response only in contrast enhancing gliomas. [2-5] Non-enhancing tumors or tumor compartments do not appear to respond to bevacizumab, which reflects the independence of vascular endothelial growth factor mediated angiogenesis. Disease progression following response to bevacizumab in high grade gliomas most often appears as an increasing nonenhancing tumor as reflected by increased MRI FLAIR signal. [2-5]
Tallibert et al. state that response to bevacizumab is independent of 1p19q status and other data show it is also independent of number of recurrences. Irrespective of up-front treatment, overall survival of 1p19q co-deleted anaplastic oligodendroglial tumors does appear superior to uni- or non-deleted tumors based on two randomized clinical trials. [1-3] Co-deletion confers a more favorable outcome and is a prognostic variable reflecting less aggressive tumor biology and improved response to treatment.
References
1. Tallibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology 2009; 72:1601-1606.
2. Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol 2009; 91:359–367.
3. Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer 2009; 115: 1734-1743.
4. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008; 70:779–787.
5. Desjardins A II, Reardon DA, Herndon JE, et al. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res 2008; 14:7068–7073.
Editor’s Note: The authors of the article were offered the opportunity to respond but declined.
Disclosure: Dr. Chamberlain received honoraria from serving on the scientific advisory board of Schering-Plough, Genentech and Enzon; received honoraria/travel for serving on the speaker's bureau of Schering-Plough, Genentech and Enzon; serves as an editorial board member of CNS Drugs.
We commend Tallibert et al. for their article regarding the efficacy of bevacizumab and irinotecan for recurrent oligodendroglial tumors. [1]
Bevacizumab was recently approved for treatment of recurrent glioblastoma by the US Food and Drug Administration. It was approved as a single agent because there is no data showing a survival benefit in combining it with irinotecan. Furthermore, irinotecan adds both cost and toxicity. These issues are relevant to the retrospective study by Tallibert al. because data regarding the added benefit of combining irinotecan with bevacizumab for recurrent anaplastic gliomas (AG) is equally uncertain.
We investigated the use of single agent bevacizumab for both recurrent anaplastic astrocytoma and anaplastic co-deleted oligodendrogliomas and saw similar outcomes with respect to overall response rate, mPFS, and 6-month progression free survival. [2, 3] Our data, similar to that for recurrent glioblastoma, do not indicate any value in adding irinotecan to bevacizumab for recurrent AG. A prospective trial of bevacizumab with or without irinotecan for recurrent AG is needed to adjudicate this issue.
Tallibert et al. treated seven patients with World Health Organization grade 2 tumors that appeared to have dedifferentiated by neuroradiology into grade 3 tumors. Whether transformation into a higher grade can be determined by anatomic MR imaging is debatable. In addition, whether low grade gliomas respond to bevacizumab is uncertain although available data suggests response only in contrast enhancing gliomas. [2-5] Non-enhancing tumors or tumor compartments do not appear to respond to bevacizumab, which reflects the independence of vascular endothelial growth factor mediated angiogenesis. Disease progression following response to bevacizumab in high grade gliomas most often appears as an increasing nonenhancing tumor as reflected by increased MRI FLAIR signal. [2-5]
Tallibert et al. state that response to bevacizumab is independent of 1p19q status and other data show it is also independent of number of recurrences. Irrespective of up-front treatment, overall survival of 1p19q co-deleted anaplastic oligodendroglial tumors does appear superior to uni- or non-deleted tumors based on two randomized clinical trials. [1-3] Co-deletion confers a more favorable outcome and is a prognostic variable reflecting less aggressive tumor biology and improved response to treatment.
References
1. Tallibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology 2009; 72:1601-1606.
2. Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol 2009; 91:359–367.
3. Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer 2009; 115: 1734-1743.
4. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008; 70:779–787.
5. Desjardins A II, Reardon DA, Herndon JE, et al. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res 2008; 14:7068–7073.
Editor’s Note: The authors of the article were offered the opportunity to respond but declined.
Disclosure: Dr. Chamberlain received honoraria from serving on the scientific advisory board of Schering-Plough, Genentech and Enzon; received honoraria/travel for serving on the speaker's bureau of Schering-Plough, Genentech and Enzon; serves as an editorial board member of CNS Drugs.