International Journal of Pediatric Otorhinolaryngology 61 (2001) 135–142 Efficacy of topotecan treatment on an experimental model of transient evoked otoacoustic emissions Nuray Bayar a, *, Bilgehan Bo ¨ke b , Alpaslan Apan c , M. Can Koc ¸ a a ENT Department, Faculty of Medicine, Kirikkale Uniersity, Kirikkale, Turkey b ENT Department, Faculty of Medicine, Hacettepe Uniersity, Hacettepe, Turkey c Anaesthesiology and Reanimation Department, Faculty of Medicine, Kirikkale Uniersity, Kirikkale, Turkey Received 19 May 2001; received in revised form 20 August 2001; accepted 21 August 2001 Abstract Objectie: The aim of this study was to investigate the effects of topotecan (Hycamtin ® ), a topoisomerase I inhibiting anticancer agent, on Transient Evoked Otoacoustic Emissions (TEOAEs) of the rabbits. We planned to investigate whether this test might provide a method for monitoring early ototoxic influence of drug administration to the cochlea. Methods: The study was conveyed in two groups each consisting of five rabbits with a total of ten ears. Rabbits in group I received i.v. topotecan (0.5 mg/kg once daily) for 3 days. Rabbits in group II received i.v. topotecan (0.25 mg/kg once daily) for 3 days. Cochlear function was serially monitored using transient evoked otoacoustic emissions before administration (BA) and on the 4th and 15th days after administration of topotecan. TEOAEs were analysed in terms of mean stimulus, stability and emission amplitude at 1.0 – 4.0 kHz. Results: For group I and II, intergroup and intragroup differences were not statistically significant in the mean stimulus, stability and emission amplitudes at 1.0–4.0 kHz. Conclusions: We evaluated the potential role of TEOAEs in early identification of cochlear dysfunction induced by topotecan. It was concluded that topotecan did not have ototoxic effects on the cochlea in the early period of administration. TEOAEs may be useful to monitor the cochlear function and to detect the late stage of ototoxicity especially in the presence of potentially toxic factors for the prevention of permanent damage. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Topotecan; TEOAEs; Rabbits www.elsevier.com/locate/ijporl 1. Introduction Topotecan, a new anticancer agent [1], is an anolog of camptothecin [2]. It is known as to- poisomerase I inhibiting agent [1]. Topoisomerase I enzyme is intimately involved in DNA replica- tion [3]. Topoisomerase I normally breaks and then reseals a single strand of DNA thus relieving the torsional strain that occurs during DNA tran- scription and replication [4]. Topotecan stabilizes the Topoisomerase I – DNA complex, inhibiting topoisomerase I function or initiates events that * Corresponding author. Present address: Kuzgun Sok. Orkide Apt. No: 50/13, 06540 As ¸ag ˘ı Ayranci/Ankara, Turkey. Tel.: +90-312-4689347; fax: +90-318-2252819. E-mail address: nurayb@hotmail.com (N. Bayar). 0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0165-5876(01)00578-X