Keynote Lecture

Prof. Göran Laurell
Department of surgical sciences, ENT section, Uppsala university, Sweden

Pharmacological intervention in the field of ototoxicity

Modern research on ototoxicity goes back to the 1940s when streptomycin was introduced into clinical practice. Today aminoglycoside antibiotics and platinum-based chemotherapy, mainly cisplatin, are the most important drugs that damage the inner ear and cause hearing loss. The ototoxic effects, especially those produced by cisplatin treatment, limit its clinical use. The mode of drug administration influences on the possibility to perform adequate monitoring of drug pharmacokinetics. Aminoglycoside antibiotics are normally given by repeated daily dosages while cisplatin is administered less frequently. Plasma concentration of gentamicin and amikacin are routinely measured in patients. Free and active cisplatin is more difficult to assess and cisplatin plasma concentration measurements are not used in clinical practice. It is not possible to calculate the risk of an ototoxic effect but a simple and useful way to avoid an ototoxic lesion of cisplatin is dose reduction. However, a lower dose may be associated with a reduced antineoplastic effect. Nevertheless, it is an important ethical principle to mitigate risks and avoid complications in patients.

There are many studies going on with the aim to discover and develop drugs to treat different types of inner ear disorders. One major limitation in clinical practice is the diagnostic procedures insufficient to diagnose inner ear disorders at a subcellular level. The mechanisms of ototoxicity and subsequent loss of hearing function have been mapped in different types of experimental models and provided us with information useful for developing protective treatment. Concomitant administration of an otoprotector is an attractive approach to avoid ototoxicity. When an ototoxic lesion is established restoration of hearing function will be more difficult. For cisplatin a large number of otoprotectors has been suggested. In clinical trials to circumvent the ototoxic effect no treatment has so far been successful. Some of these aspects on pharmacological intervention in the field of ototoxicity will be highlighted during the lecture.