Cisplatin is a chemotherapeutic agent commonly used to treat a variety of cancer types, but its use comes with a risk of hearing impairment or ototoxicity. Researchers from the University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center in Pennsylvania recently reviewed cisplatin-induced ototoxicity, which was published in the journal JCO Oncology Practice.
The researchers explained that cisplatin and other platinum-based chemotherapeutic agents are the most common types of agents used in chemotherapy for solid malignancies, with at least 500,000 patients in the US each year being potential candidates for cisplatin treatment. However, incidence of ototoxicity in adults and some level of hearing impairment in pediatric patients, estimated at 36% and 40% to 60%, respectively, are associated with its use.
Overall, hearing impairment shows a 5-fold higher risk with cisplatin use. “Ototoxicity can manifest as tinnitus, hearing loss in the high-frequency range (4000 to 8000 Hz), or at late stages, a decreased ability to hear in the lower-frequency normal conversation range,” the researchers reported.
Determining the mechanism behind this adverse effect could possibly aid in developing strategies to mitigate it. Potential mechanisms for cisplatin-induced ototoxicity include direct cytotoxicity from the platinum-containing agent, direct damage to DNA, or induction of apoptosis through mechanisms involving cell cycle arrest and/or generation of reactive oxygen species.
Evidence for optimal prevention and management strategies related to cisplatin-induced ototoxicity is limited. The researchers performed a literature review and surveyed practicing oncologists within the UPMC Hillman Cancer Center network to evaluate recommendations in the published literature within the context of real-world practice. Of 120 clinicians surveyed, 35 identified a lack of standardized monitoring guidelines and effective prevention strategies as crucial limitations.
Overall, standardized guidelines from the literature regarding monitoring, prevention, and management of cisplatin-induced ototoxicity appeared to be limited, particularly for adults with cancer. Oncologists in practice also seemed to use a variety of approaches to manage cisplatin-induced ototoxicity, reinforcing the potential usefulness of guidelines for managing this condition. Nearly all respondents (97%) reported that they discuss the risk of ototoxicity with their patients prior to cisplatin treatment, but practices for monitoring ototoxicity varied widely.
Management of cisplatin-induced ototoxicity is also limited by the lack of regulatory approval for many approaches. Most agents under discussion for reducing or reversing cisplatin-induced ototoxicity remain investigational. However, in 2022, the US FDA approved sodium thiosulfate (STS) for the reduction of ototoxicity risk associated with cisplatin in pediatric patients aged 1 month and older who have localized, nonmetastatic solid tumors.
“The recent approval of STS by the FDA to treat ototoxicity in pediatric patients with localized, nonmetastatic solid tumors greenlights the need for further testing of similar agents in adult patients,” the researchers wrote in their report.
Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Chattaraj A, Syed MP, Low CA, Owonikoko TK. Cisplatin-induced ototoxicity: a concise review of the burden, prevention, and interception strategies. JCO Oncol Pract. Published online March 15, 2023. doi:10.1200/OP.22.00710