Tapered dose versus constant drug exposure to anti-EGFR drugs on head-and-neck cancer xenografts. A comparison between cetuximab and gefitinib☆
Summary
Head-and-neck (H&N) tumor re-growth is clinically observed after arrest of anti-EGFR therapies. In the present study, we compared, for a similar dose exposure to anti-EGFR therapies, constant (CS) with tapered (TS) schedules (i.e. progressive dose reduction) for cetuximab, a mAb, and gefitinib, a TKI.
Mice bearing CAL33 H&N tumors with high EGFR content were treated with cetuximab or gefitinib. CS consisted of 7
days of cetuximab or gefitinib administration and TS of 7
days of drugs followed by 7
days of administration at decreased doses (divided by 2 every day).
Gefitinib TS but not CS slowed down tumor re-growth. Cetuximab TS had a stronger and longer-lasting effect than CS, paralleled by a down-regulation of EGFR expression.
Whatever the drug, TS decreased tumor re-growth more efficiently than CS. This new drug schedule could be of interest in the management of anti-EGFR based therapies in H&N cancer.
Keywords: Head-and-neck cancer, Gefitinib, Cetuximab, Dose modulation
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☆ Results presented in part during the 2008 annual meeting of the American Association for Cancer Research (AACR).
PII: S1368-8375(09)00979-8
doi:10.1016/j.oraloncology.2009.11.010
© 2009 Elsevier Ltd. All rights reserved.
