Cisplatin-Induced Hearing Loss

Childhood Cancer Hearing Loss Patient Focused Drug Development (PFDD) Meeting

The pediatric patient population with chemotherapy-induced hearing loss represents a segment of the cancer survivor community with a severe burden of disease with great unmet medical need. An externally led, FDA-approved Patient Focused Drug Development (PFDD) meeting on September 13, 2018, near Washington, DC, explored these issues in depth.

Overview of cisplatin-induced ototoxicity

When soundwaves travel through the inner ear, they stimulate sensory hair cells which trigger the nervous system to communicate with the auditory cortex of the brain. Platinum-based therapies like cisplatin can cause ototoxicity by damaging these hair cells which cannot regrow. This can result in irreversible hearing loss.1

Cisplatin is considered a cornerstone of treatment for many solid tumor cancers. However, an unfortunate side effect of its use is irreversible ototoxicity (or hearing loss).2 In fact, 60% to 90% of patients treated with cisplatin have been reported to develop hearing loss.2,3,4 Cisplatin induced ototoxicity (CIO) poses significant challenges across all age groups. Because this is a dose-limiting toxicity, the risk increases alongside the amount of cisplatin administered.2 The impact of ototoxicity may be permanent, severe, and profound—with the potential to significantly impact quality of life as well as many aspects of daily life, such as speech and language skills, academic performance, social-emotional development, career potential & the ability to live independently.1

Current interventions such as hearing aids are implemented after hearing loss has occurred. They do not replace normal hearing and can be challenging for children particularly to use.1 The overall survival rate for some cancers treated with cisplatin can reach up to ~87%, making the permanent and progressive impact of ototoxicity an important consideration.5,6

Understanding how cisplatin-induced ototoxicity occurs

  • Cisplatin carries the highest risk of ototoxicity among all FDA-approved platinum-based chemotherapies.
  • Cisplatin-induced ototoxicity is characterized by the production of toxic levels of reactive oxygen species within the cochlea, resulting in the destruction of cochlear hair cells and damage to the stria vascularis and spiral ganglion cells1
  • Once cochlear hair cells are destroyed, they cannot grow back1
    • This damage is generally dose dependent, bilateral (affecting both sides), and irreversible1
    • The resulting hearing loss can also be accompanied by tinnitus and vertigo1

Learn more about cisplatin-induced hearing loss

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Recognizing the signs and symptoms

Signs and symptoms seen in children as ototoxicity develops include:

  • High-frequency (≥4 kHz) sensorineural hearing loss that is bilateral (affecting both sides), progressive, and irreversible1,2,7
  • Progression of hearing loss to involve lower frequencies (<4 kHz)
  • Tinnitus1,2
  • Vertigo1,2
  • Hearing loss that can continue to progress due to prolonged retention of platinum after completion of therapy2

Onset can occur early into treatment with cisplatin

  • Just 1 cisplatin treatment cycle can lead to a lifetime of hearing loss2
  • Hearing can deteriorate for years after treatment is over2,10

The impact of ototoxicity can be lifelong and severe

  • Progressive and irreversible hearing loss can have a profound impact on children1,2,8,9
  • The burden of hearing loss exerts a toll on many crucial aspects of their life, such as8:
    • Speech and language skills
    • Social-emotional development
    • Academic performance
  • For adolescents and young adults, hearing loss is associated with9:
    • Depression
    • Underemployment
    • Reduced earnings
    • Social functioning problems
    • Not graduating high school
    • Not living independently
    • Never marrying

Non-pharmacological interventions are not preventative

  • Non-pharmacological interventions are implemented after hearing loss has occurred1
  • Hearing aids
    • Do not restore normal hearing1
    • Unable to separate speech and noise in noisy environments1
    • Daily use and care may be challenging for children1
    • Those with ototoxic hearing loss are more likely to benefit from advances in technology like extended bandwidth hearing aids or hearing aids with frequency-lowering technology3
    • Most insurance plans don’t cover the cost of hearing aids, which will need to be replaced & don’t restore normal hearing.11
  • Cochlear implants
    • A surgically implanted neuro-prosthetic device to provide a modified sense of sound for moderate to profound sensorineural hearing loss1
    • Require commitment to audiology and speech therapy rehabilitation programs1

References:

  1. Landier W. Ototoxicity and cancer therapy. Cancer. 2016;122(11):1647-1658.
  2. Langer T, am Zehnhoff-Dinnesen A, Radtke S, et al. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci. 2013;34(8):458-469.
  3. Paken J, Govender CD, Pillay M, Sewram V. Cisplatin-associated ototoxicity: a review for the health professional. J Toxicol. 2016;2016:1809394.
  4. Sprauten M. J. Clin Oncol. 2012;30:300-307
  5. Hennegan K, Silber A, Dehipawala S, Chithran K, Lockhart D. Evaluating the burden of survival of platinum-induced hearing loss in pediatric solid tumor patients: a systematic literature review. ISPOR Annual Meeting 2020. May 18-20, 2020 [Virtual]. Poster PIH67.
  6. Freyer DR, Brock PR, Chang KW, et al. Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline. Lancet Child Adolesc Health. 2020;4(2):141-150.
  7. Waissbluth S, Del Valle A, Chuang A, Becker A. Incidence and associated risk factors for platinum-induced ototoxicity in pediatric patients. Int J Pediatr Otorhinolaryngol. 2018;111:174-179.
  8. Clemens E, van den Heuvel-Eibrink MM, Mulder RL, et al. Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium. Lancet Oncol. 2019;20(1):e29-e41.
  9. Bass JK, Knight KR, Yock TI, et al. Evaluation and management of hearing loss in survivors of childhood and adolescent cancers: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2016;63(7):1152-1162.
  10. Breglio AM et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017 Nov 21;8(1):1654.
  11. Blustein J, Weinstein BE. Opening the Market for Lower Cost Hearing Aids: Regulatory Change Can Improve the Health of Older Amer­icans. Am J public Health. 2016 Jun;106(6):1032-5.