Andrew DNorden, Brigham and Women's Hospital, 44 Binney St, Boston, MA 02115anorden@partners.org
Geoffrey S. Young, Patrick Y. Wen
Submitted June 04, 2008
We thank Drs. Chamberlain and Mrugala for their thoughtful comments. A major challenge in treating patients with recurrent malignant gliomas in the era of anti-angiogenic therapy involves the assessment of tumor response and progression on MRI scans.
Macdonald criteria for determining response and progression, described in 1990 before anti-angiogenic treatments were available, rely exclusively on the maximal cross-sectional area of enhancing tumor. [8] This approach is problematic if widely used treatments such as bevacizumab effectively control contrast enhancement but permit non-enhancing, infiltrative recurrence.
In response to Dr. Chamberlain’s query regarding overall survival in the cytotoxic chemotherapy group, there was no significant overall survival difference between the two cohorts.
In addition to the Notch ligand Delta-like 4 (DLL4), pro-angiogenic signaling molecules that may play a role in resistance to anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor therapies include basic fibroblast growth factor (bFGF) and stromal-derived factor 1-alpha (SDF1-alpha) [5], among many others. [9]
Inhibition of these targets may potentiate the effects of currently available anti-angiogenic therapies and translate into improved outcomes for patients with these devastating tumors.
References
8. Macdonald DR, Cascino TL, Schold SC, Jr., Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277–1280.
9. Chi A, Norden AD, Wen PY. Inhibition of angiogenesis and invasion in malignant gliomas. Expert Rev Anticancer Ther 2007;7:1537-1560.
Disclosures: P.Y. Wen receives research support from Genentech, Inc. The other authors report no disclosures.
We thank Drs. Chamberlain and Mrugala for their thoughtful comments. A major challenge in treating patients with recurrent malignant gliomas in the era of anti-angiogenic therapy involves the assessment of tumor response and progression on MRI scans.
Macdonald criteria for determining response and progression, described in 1990 before anti-angiogenic treatments were available, rely exclusively on the maximal cross-sectional area of enhancing tumor. [8] This approach is problematic if widely used treatments such as bevacizumab effectively control contrast enhancement but permit non-enhancing, infiltrative recurrence.
In response to Dr. Chamberlain’s query regarding overall survival in the cytotoxic chemotherapy group, there was no significant overall survival difference between the two cohorts.
In addition to the Notch ligand Delta-like 4 (DLL4), pro-angiogenic signaling molecules that may play a role in resistance to anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor therapies include basic fibroblast growth factor (bFGF) and stromal-derived factor 1-alpha (SDF1-alpha) [5], among many others. [9]
Inhibition of these targets may potentiate the effects of currently available anti-angiogenic therapies and translate into improved outcomes for patients with these devastating tumors.
References
8. Macdonald DR, Cascino TL, Schold SC, Jr., Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990;8:1277–1280.
9. Chi A, Norden AD, Wen PY. Inhibition of angiogenesis and invasion in malignant gliomas. Expert Rev Anticancer Ther 2007;7:1537-1560.
Disclosures: P.Y. Wen receives research support from Genentech, Inc. The other authors report no disclosures.