title: The influence of inhibition of the epidermal growth factor receptor on tympanic membrane wound healing in rats.
abstract: Recently, a report on a bilateral tympanic membrane (TM) perforation in a patient after long-term treatment with erlotinib was published. The object of this study was to investigate the destructive potential of topical applied epidermal growth factor receptor (EGFR) inhibitors on wound healing of experimental TM perforation in rats by evaluating closure rates and histology. In 12 rats, erlotinib (10&#x00A0;mg/ml) was applied to one TM of each animal and cetuximab (5&#x00A0;mg/ml) to the other side daily for 12 consecutive days. Both the erlotinib group (11.8 days) and cetuximab group (9 days) had prolonged healing latencies compared to a reference value (7 days). We observed differences in the histologic parameters between both groups. Our results suggest that in normal TM, the inhibition of EGFR does not lead to a persistent perforation. However, in case of preexisting TM pathology, a spontaneous perforation in patients under long-term treatment of EGFR inhibitors seems to be possible.
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, University of Greifswald, Walther-Rathenau-Strasse 43-45, 17475, Greifswald, Germany. holger.kaftan@uni-greifswald.de
authors.forename: Holger
authors.initials: H
authors.lastname: Kaftan
authors.forename: Lars
authors.initials: L
authors.lastname: Reuther
authors.forename: Bärbel
authors.initials: B
authors.lastname: Miehe
authors.forename: Werner
authors.initials: W
authors.lastname: Hosemann
authors.forename: Michael
authors.initials: M
authors.lastname: Herzog
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000068818:Cetuximab; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014432:Tympanic Membrane / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D018058:Tympanic Membrane Perforation / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab