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

Abstract

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.

• Authors: Christine H Chung, Paula R Pohlmann, Mace L Rothenberg, Brian B Burkey, Joel Parker, Kevin Palka, Joseph Aulino, Igor Puzanov, Barbara Murphy
• Journal: Head & neck (Head Neck) Vol. 33 Issue 12 Pg. 1804-8 (Dec 2011) ISSN: 1097-0347 [Electronic] United States
• PMID: 20652976 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• ganitumab
• Receptor, IGF Type 1
• Cetuximab
• Methotrexate

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy)
• Cetuximab
• Female
• Head and Neck Neoplasms (drug therapy)
• Humans
• Methotrexate (therapeutic use)
• Middle Aged
• Receptor, IGF Type 1 (antagonists & inhibitors)