Cetuximab and bevacizumab: Preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck

A. Argiris, A. P. Kotsakis, T. Hoang, F. P. Worden, P. Savvides, M. K. Gibson, R. Gyanchandani, G. R. Blumenschein, H. X. Chen, J. R. Grandi, P. M. Harari, M. S. Kies, S. Kim

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Background: We evaluated combined targeting with cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: The combination was studied in human endothelial cells and head and neck and lung cancer xenograft model systems. Patients with recurrent or metastatic SCCHN were treated with weekly cetuximab and bevacizumab, 15 mg/kg on day 1 given intravenously every 21 days, until disease progression. Analysis of tumor biomarkers and related serum cytokines was performed. Results: Cetuximab plus bevacizumab enhanced growth inhibition both in vitro and in vivo, and resulted in potent reduction in tumor vascularization. In the clinical trial, 46 eligible patients were enrolled. The objective response rate was 16% and the disease control rate 73%. The median progression-free survival and overall survival were 2.8 and 7.5 months, respectively. Grade 3-4 adverse events were expected andoccurred in less than 10% of patients. transforming growth factor alpha, placenta-derived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy. Conclusions: Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients withSCCHN.

Original languageEnglish (US)
Article numbermds245
Pages (from-to)220-225
Number of pages6
JournalAnnals of Oncology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2013

    Fingerprint

Keywords

  • Bevacizumab
  • Cetuximab
  • EGFR
  • Head
  • Neck cancer
  • VEGF

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Argiris, A., Kotsakis, A. P., Hoang, T., Worden, F. P., Savvides, P., Gibson, M. K., Gyanchandani, R., Blumenschein, G. R., Chen, H. X., Grandi, J. R., Harari, P. M., Kies, M. S., & Kim, S. (2013). Cetuximab and bevacizumab: Preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Annals of Oncology, 24(1), 220-225. [mds245]. https://doi.org/10.1093/annonc/mds245