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

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: The efficacy of this combination of sunitinib, cetuximab and RT may be of clinical importance in the management of head and neck cancer patients.