Tapered dose versus constant drug exposure to anti-EGFR drugs on head-and-neck cancer xenografts. A comparison between cetuximab and gefitinib

Abstract

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.