Tapered dose versus constant drug exposure to anti-EGFR drugs on head-and-neck cancer xenografts. A comparison between cetuximab and gefitinib.
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.
Bozec
Alexandre
A
Centre Antoine-Lacassagne, Nice, France.
Formento
Patricia
P
Fischel
Jean-Louis
JL
Etienne-Grimaldi
Marie-Christine
MC
Milano
Gérard
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011799:Quinazolines / Q000008:administration & dosage*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000068818:Cetuximab; D000077156:Gefitinib