Jean-Pascal Machiels1, Sandra Schmitz. 1. Centre du Cancer, Department of Medical Oncology, Clinique de cancérologie cervico-maxillo-faciale, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium. jean-pascal.machiels@uclouvain.be
Abstract
PURPOSE OF REVIEW: Cetuximab improves the overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN), in combination either with radiation therapy or with chemotherapy. However, only a minority of patients seem to benefit from cetuximab. This paper will review the different strategies developed either to overcome epidermal growth factor receptor (EGFR) resistance or to inhibit the other relevant activated molecular pathways. RECENT FINDINGS: Recent trials have investigated the possibility of including anti-EGFR therapies in the multimodal curative treatment of SCCHN in combination with neoadjuvant chemotherapy, concomitant chemoradiation or as maintenance therapy. Second-generation compounds (pan-HER or dual EGFR/HER-2 tyrosine kinase inhibitors) have been designed in an attempt to overcome the postulated resistance to anti-EGFR treatments in SCCHN. Alternative targeted therapies have also been developed to inhibit the other activated molecular pathways. Some of these new treatments have shown either promising activity in preclinical models or interesting preliminary activity in early phase II trials. Phase III trials are now required to validate the findings. SUMMARY: Despite an aggressive multimodal approach, more than 50% of patients with SCCHN will relapse. It is therefore essential that targeted agents continue to be evaluated in this disease in the hope of improving outcome.
PURPOSE OF REVIEW: Cetuximab improves the overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN), in combination either with radiation therapy or with chemotherapy. However, only a minority of patients seem to benefit from cetuximab. This paper will review the different strategies developed either to overcome epidermal growth factor receptor (EGFR) resistance or to inhibit the other relevant activated molecular pathways. RECENT FINDINGS: Recent trials have investigated the possibility of including anti-EGFR therapies in the multimodal curative treatment of SCCHN in combination with neoadjuvant chemotherapy, concomitant chemoradiation or as maintenance therapy. Second-generation compounds (pan-HER or dual EGFR/HER-2 tyrosine kinase inhibitors) have been designed in an attempt to overcome the postulated resistance to anti-EGFR treatments in SCCHN. Alternative targeted therapies have also been developed to inhibit the other activated molecular pathways. Some of these new treatments have shown either promising activity in preclinical models or interesting preliminary activity in early phase II trials. Phase III trials are now required to validate the findings. SUMMARY: Despite an aggressive multimodal approach, more than 50% of patients with SCCHN will relapse. It is therefore essential that targeted agents continue to be evaluated in this disease in the hope of improving outcome.
Authors: Paul A Clark; Mari Iida; Daniel M Treisman; Haviryaji Kalluri; Sathyapriya Ezhilan; Michael Zorniak; Deric L Wheeler; John S Kuo Journal: Neoplasia Date: 2012-05 Impact factor: 5.715
Authors: Ranee Mehra; Ilya G Serebriiskii; Roland L Dunbrack; Matthew K Robinson; Barbara Burtness; Erica A Golemis Journal: Drug Resist Updat Date: 2011-09-14 Impact factor: 18.500
Authors: Trisha M Wise-Draper; David J Draper; J Silvio Gutkind; Alfredo A Molinolo; Kathryn A Wikenheiser-Brokamp; Susanne I Wells Journal: Transl Res Date: 2012-02-28 Impact factor: 7.012
Authors: Boban M Erovic; Luke Harris; Mina Jamali; David P Goldstein; Jonathan C Irish; Sylvia L Asa; Ozgur Mete Journal: Endocr Pathol Date: 2012-12 Impact factor: 3.943