The impact of timing of EGFR and IGF-1R inhibition for sensitizing head and neck cancer to radiation

Anticancer Res. 2012 Aug;32(8):3029-35.

Abstract

Background: Targeting the epidermal growth factor receptor (EGFR) improved radiotherapy outcome by 10-15% in head and neck tumors (HNSCC). We tested the therapeutic benefits of co-targeting EGFR and insulin-like growth factor-1 receptor (IGF-1R) to further enhance tumor response to radiation.

Materials and methods: Mice bearing FaDu tumor xenografts were treated with ganitumab (previously known as AMG479, an anti-IGF-1R antibody), panitumumab (an anti-EGFR antibody), or both in combination with fractionated doses of radiation. Tumor growth delay and tumor cure/recurrence served as end-points.

Results: The best tumor growth delay was achieved when ganitumab and panitumumab were given concurrently with radiation. Tumor cure/recurrence studies showed that combining ganitumab, panitumumab and radiation resulted in significantly higher radiocurability rates than use of either of the agents given with radiation.

Conclusion: These findings provide the rationale for clinical testing of the combination of ganitumab and panitumumab for the treatment of HNSCC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Dose Fractionation, Radiation
  • ErbB Receptors / antagonists & inhibitors*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Mice
  • Panitumumab
  • Radiation Tolerance*
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Panitumumab
  • ganitumab
  • ErbB Receptors
  • Receptor, IGF Type 1