Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts

Shousong Cao; Farukh A. Durrani; Karoly Toth; Youcef M. Rustum; Mukund Seshadri

doi:10.1016/j.oraloncology.2011.04.001

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Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts

Journal article

Peer reviewed

Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts

Shousong Cao, Farukh A. Durrani, Karoly Toth, Youcef M. Rustum and Mukund Seshadri

Oral oncology, Vol.47(6), pp.459-466

2011

DOI: 10.1016/j.oraloncology.2011.04.001

PMCID: PMC3109241

PMID: 21530364

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Abstract

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 20 mg/kg) to nude mice bearing FaDu HNSCC xenografts for 28 days with the first dose beginning seven days prior to Irinotecan (100 mg/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 (5 mg/kg) while high dose Bevacizumab (20 mg/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 (5 mg/kg/day × 28 days) in combination with Irinotecan (100 mg/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.

Bevacizumab

Combination therapy

Head and neck cancer

Human tumor xenografts

Irinotecan

MRI

Details

Title: Subtitle: Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts
Creators: Shousong Cao - Roswell Park Cancer Institute
Farukh A. Durrani - Roswell Park Cancer Institute
Karoly Toth - Roswell Park Cancer Institute
Youcef M. Rustum - Roswell Park Cancer Institute
Mukund Seshadri - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Oral oncology, Vol.47(6), pp.459-466
DOI: 10.1016/j.oraloncology.2011.04.001
PMID: 21530364
PMCID: PMC3109241
NLM abbreviation: Oral Oncol
ISSN: 1368-8375
eISSN: 1879-0593
Publisher: Elsevier Ltd
Language: English
Date published: 2011
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359798602771

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