Combining
antiangiogenic agents with traditional cytotoxic
chemotherapy offers the potential to target both vascular and cellular components of a growing
tumor mass. Here, we examined the antitumor activity of the
vascular endothelial growth factor antibody,
Bevacizumab (Avastin®) in combination with the
topoisomerase I inhibitor,
Irinotecan (CPT-11) against human
head and neck squamous cell carcinoma (
HNSCC) xenografts.
Bevacizumab was administered daily (at 5 or 20mg/kg) to nude mice bearing FaDu
HNSCC xenografts for 28days with the first dose beginning seven days prior to
Irinotecan (100mg/kg, weekly × 4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and immunohistochemical (IHC) methods were employed to study the antiangiogenic effects of
Bevacizumab in vivo. Kinetics of
tumor response to treatment was studied by monitoring
tumor volume over a 60-day period. DCE-MRI detected a significant reduction in vascular permeability following treatment with
Bevacizumab (5mg/kg) while high dose
Bevacizumab (20mg/kg) induced significant microvascular damage and
tumor necrosis, confirmed by immunohistochemistry (IHC).
Irinotecan alone resulted in complete
tumor regression (cures) in ∼40% of animals while
Bevacizumab alone did not result in any cures. Treatment with
Bevacizumab (5mg/kg/day×28days) in combination with
Irinotecan (100mg/kg, weekly × 4) was highly effective in inhibiting FaDu
tumor growth and resulted in complete
tumor regression in 80% of animals. These results demonstrate that long term administration of
Bevacizumab effectively modulates chemotherapeutic efficacy against
HNSCC xenografts. Further investigation into the therapeutic potential of this combination strategy against
HNSCC is warranted.