Combination of sunitinib, cetuximab and irradiation in an orthotopic head and neck cancer model

Recent preclinical and clinical studies indicate beneficial effects from combining radiotherapy with either anti-angiogenic drugs or anti-epidermal growth factor receptor (EGFR)-targeting agent. To investigate the effect of combining these approaches, we evaluated in vivo the antitumor efficacy of t...

Full description

Saved in:

Bibliographic Details
Published in:	Annals of oncology Vol. 20; no. 10; pp. 1703 - 1707
Main Authors:	Bozec, A., Sudaka, A., Toussan, N., Fischel, J.-L., Etienne-Grimaldi, M.-C., Milano, G.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-10-2009 Oxford University Press Oxford Publishing Limited (England)
Subjects:	Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal, Humanized Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Cell Line, Tumor Cetuximab Combined Modality Therapy Disease Models, Animal Drug Evaluation, Preclinical Female head and neck cancer Head and Neck Neoplasms - drug therapy Head and Neck Neoplasms - radiotherapy Humans Indoles - administration & dosage irradiation Medical sciences Mice Mice, Nude Neoplasm Transplantation Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Pharmacology. Drug treatments Pyrroles - administration & dosage Radiotherapy - methods Sunitinib Transplantation, Heterologous Tumors Xenograft Model Antitumor Assays - methods sunitinib cetuximab head and neck cancer irradiation Antineoplastic agent Orthotopic Enzyme Tyrosine kinase inhibitor Transferases Enzyme inhibitor Monoclonal antibody Malignant tumor Epidermal growth factor receptor Sunitinib Irradiation ENT disease Head and neck cancer Models Multikinase inhibitor Antiangiogenic agent Cetuximab Protein-tyrosine kinase Cancer
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Recent preclinical and clinical studies indicate beneficial effects from combining radiotherapy with either anti-angiogenic drugs or anti-epidermal growth factor receptor (EGFR)-targeting agent. To investigate the effect of combining these approaches, we evaluated in vivo the antitumor efficacy of the anti-angiogenic compound sunitinib, an oral, multi-targeted tyrosine kinase inhibitor that inhibits among others vascular endothelial growth factor (VEGF) receptors-1, -2 and -3, cetuximab, a mAb targeting the EGFR, and irradiation (RT) given alone and in combination. Investigations were carried out using a VEGF-secreting human head and neck tumor cell line, CAL33, with a high EGFR content, growing as orthotopic xenografts in nude mice. Three days after tumor cell injection, sunitinib (20 mg/kg, p.o.), cetuximab (1 mg/kg, i.p.), both 5 days/week seven doses, and RT (6 Gy, 3 days/week, four doses) were administered alone and in combination during 9 days. Concomitant administration of drugs produced a marked and significant supra-additive decrease, and the addition of RT completely abolished tumor growth. The drug association markedly reduced tumor cell proliferation (Ki67) and the number of the vessels, but enhanced cell differentiation. The efficacy of this combination of sunitinib, cetuximab and RT may be of clinical importance in the management of head and neck cancer patients.
Bibliography:	ark:/67375/HXZ-JQMT4VHD-V istex:A44AE6784C0886D326D79AA40F9A55B8D43BDCE1 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23
ISSN:	0923-7534 1569-8041
DOI:	10.1093/annonc/mdp070