Ototoxicity and Cancer Therapy

Certain types of antineoplastic therapies, particularly platinum-based drugs, are particularly toxic to the ears. While this is well known to researchers and clinicians who study these treatments, many members of the toxicity community are unaware of the auditory risks posed by some cancer therapies. This brief review will serve as an introduction to the link between platinum-based cancer therapies and auditory damage, and hopefully inspire developers of new cancer therapies to consider ototoxicity in the course of preclinical development.

Chemotherapeutic and Supportive Agents Platinum-based chemotherapy drugs (cisplatin, carboplatin, oxaliplatin, and others) are widely used in adults against solid tumors of the head and neck, lung, ovary, testicle, and bladder, and in children against neuroblastomas, osteosarcomas, hepatoblatomas, germ cell tumors, and CNS tumors. Primarily through the generation of reactive oxygen species, platinum-based agents, especially cisplatin, lead to irreversible loss of hair cells, damage to the stria vascularis, spiral ganglion cells, and resulting sensorineural hearing loss. The risk is generally higher in children, as well as patients with CNS tumors, decreased renal function, and treatment with other ototoxic agents. The overall prevalence of ototoxicity ranges widely, but reaches 90% in high-risk groups (Landier et al, 2014), and suggests a potential genetic susceptibility in some patients.

Chemotherapeutic agents are not the only drugs that present ototoxic risks to cancer patients. Common supportive therapies for cancer patients, such as aminoglycoside antibiotics and loop diuretics, also have potential to affect hearing. Aminoglycoside antibiotics also generate reactive oxygen species and subsequent irreversible hearing loss. Loop diuretics affect fluids and electrolyte concentrations in the inner ear, and generally lead to reversible hearing loss. However, the collective ototoxic potential of chemotherapeutic and supportive therapies increases when they are administered together.

Detection of Ototoxicity Turner Scientific offers a full spectrum of ototoxic assessments for preclinical studies of antineoplastic and other drugs. Behavioral audiometry is often the initial testing to be done, and can accurately detect hearing loss and tinnitus in a cost-effective and timely manner. Electrophysiologic and histologic testing usually accompanies behavioral audiometry, and determines the effect of cancer drugs on the conduction of sound impulses through higher brain regions, and the survival of fragile hair cells and auditory nerve fibers. The FDA recommends electrophysiologic and histologic testing of any compound that reaches the cochlea, and given the known ototoxic potential of some cancer drugs, it may be prudent to assess this potential in new chemotherapeutic agents as well.

References Landier, W. (2016). Ototoxicity and cancer therapy. Cancer 122(11), 1647-1658.

Landier, W., Knight, K., Wong, F.L., Lee, J., Thomas, O., Kim H., et al. (2014). Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales – a report from the Children’s Oncology Group. J Clin Oncol 32(6), 527-539.

Authors David Hicks, M.D.: Dr. Hicks directs business development at Turner Scientific, and has significant training and experience in clinical treatment of ear disorders. Contact: dhicks@turnerscientific.com

Jeremy Turner, Ph.D.: Dr. Turner is the founder and Chief Scientific Officer at Turner Scientific. He completed his Ph.D. in auditory neuroscience, and has more than 22 years’ experience in preclinical hearing loss, tinnitus, and ototoxicity research. Contact: jturner@turnerscientific.com

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