A Review of Cisplatin-Associated Ototoxicity

Abstract

Cisplatin, an effective antineoplastic drug used in the treatment of many cancers, has ototoxic potential, thus placing cancer patients, receiving this treatment, at risk of hearing loss. It is therefore important for health care professionals managing these patients to be aware of cisplatin's ototoxic properties and its clinical signs to identify patients at risk of developing a hearing impairment. Eighty-five English peer-reviewed articles and two books, from January 1975 to July 2015, were identified from PubMed, ScienceDirect, and EBSCOhost. An overview of cisplatin-associated ototoxicity, namely its clinical features, incidence rates, molecular and cellular mechanisms, and risk factors, is presented in this article. This review further highlights the importance of a team-based approach to complement an audiological monitoring program in reducing any further loss in the quality of life of affected patients, as there is currently no otoprotective agent routinely recommended for the prevention of cisplatin-associated ototoxicity.

Regulator of G protein signaling 17 represents a novel target for treating cisplatin induced hearing loss

“…It affects almost 13–95% of children treated for neuroblastoma (assessed by CTCAE scale) 8 , even though incidence of ototoxicity was highly dependent on the auditory testing scales used. A similar wide incidence range of ototoxicity has been reported in a recent review of incidences of hearing loss in different countries 9 . Cisplatin-induced hearing loss is associated with increased cochlear cell death resulting from DNA damage, caspase activation, oxidative stress, inflammation and glutamate excitotoxicity 7 , 10 .…”

Insight into the current practice of ototoxicity monitoring during cisplatin therapy

“…Cisplatin is considered one of the most ototoxic pharmacologic agents, typically causing bilateral high frequency sensorineural hearing loss with progression to lower frequencies with continued exposure. The potential for permanent bilateral sensorineural hearing loss and tinnitus can occur both during treatment and up to 136 months after therapy completion [1][2][3][4][5][6][7][8] with an incidence of 20-84% [9,10].…”

“…A main mechanism of cisplatin ototoxicity is associated with the production of free radicals [5,6,[11][12][13]. The degree of hearing loss has been associated with cumulative dosing of platinum agents, duration of treatment, concurrent treatment with radiotherapy, history of noise exposure, and method of administrations (bolus versus infusion) [1,3,6,[9][10][11][12][13][14][15]. Evidence also suggests a genetic component to the risk factors for cisplatin-induced ototoxicity, with an estimated 38-47% [16] of individual variability linked to polymorphisms in genes encoding DNA repair enzymes and membrane pumps [11-13, 16, 17].…”

“…Hearing loss has considerable quality of life implications, with notable effects on a patient's social and emotional needs [4,6,18,19]. These impacts include safety concerns [6], communication ability [4,6,18], increased rates of depression, anxiety and social isolation [4,6,10,18], and higher incidence of hospital admission [20], compounding what is already experienced by patients diagnosed with a critical illness [4,10]. Ototoxicity monitoring programs can to a large extent avert the reduced quality of life as a result of hearing loss, since at-risk patients can be identified early, counselled, monitored and managed appropriately through a logical and systematic way [5].…”

“…Ototoxicity monitoring guidelines including those from the American Speech and Hearing Association (ASHA), and American Academy of Audiology (AAA) [21], outline an idealistic approach for ototoxicity monitoring programs [6,10]. ASHA and AAA Guidelines, established in 1994 and 2009 respectively, provide a set of broad goals for monitoring for ototoxicity including performing pretreatment baseline evaluation and counseling, monitoring visits at intervals to document hearing loss progression and follow up evaluations to determine post treatment effects.…”