Tapered dose versus constant drug exposure to anti-EGFR drugs on head-and-neck cancer xenografts. A comparison between cetuximab and gefitinib☆
Received 25 August 2009; received in revised form 20 November 2009; accepted 23 November 2009. published online 16 February 2010.
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 7days of cetuximab or gefitinib administration and TS of 7days of drugs followed by 7days 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.
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