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.


CONCLUSIONS
This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC.
Chung
Christine H
CH
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Christine.Chung@Vanderbilt.edu
Pohlmann
Paula R
PR
Rothenberg
Mace L
ML
Burkey
Brian B
BB
Parker
Joel
J
Palka
Kevin
K
Aulino
Joseph
J
Puzanov
Igor
I
Murphy
Barbara
B
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068818:Cetuximab; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C545764:ganitumab; D017526:Receptor, IGF Type 1; D000068818:Cetuximab; D008727:Methotrexate