Insulin‐like growth factor‐1 receptor inhibitor, AMG‐479, in cetuximab‐refractory head and neck squamous cell carcinoma

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG‐479 (monoclonal antibody against insulin‐like growth factor‐1 receptor [IGF‐1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board–approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF‐1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho‐IGF‐1R after treatment with AMG‐479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab‐resistance to cetuximab‐sensitivity were also observed. Conclusion This suggests that the combination of AMG‐479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010