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Late Effects



Chemotherapy Toxicity


Platinum agents, cisplatin and carboplatin, may result in irreversible high-frequency sensorineural hearing loss5.

The risk of auditory problems is increased in patients with:

  • Young age (less than 4) at time of therapy4
  • Diagnosis of CNS tumor3
  • Treatment with multiple ototoxic agents3
  • Platinum chemotherapy:
    • Progressive deficit with increasing cumulative drug dosage4
    • Rx in combination with RT to the ear or brain3
    • Decreased renal function at time of treatment20
    • Rapid IV administration of oto-toxic pharmacological agent20
    • Prolonged elevated serum trough drug level20


Hearing loss associated with platinum agents is usually3:

  • Bilateral and symmetrical
  • Associated with early symptoms:
    • Tinnitus
    • Vertigo
    • Difficulty hearing in presence of background noise
  • Secondary to vestibular injury
  • Associated with high frequency hearing loss (>2000 Hz):
    • Able to hear vowel sounds better than consonants (as low frequency sounds are mainly vowels, while high frequency sounds are mainly consonants)
    • Poor speech discrimination or perception of "hearing but not understanding"

Loss of high frequency sounds can be detrimental to children's cognitive and social development

Late hearing loss is within the speech ranges of 250-2000 Hz



Cisplatin is associated with sensorineural high frequency hearing loss and tinnitus.2

Mechanism of hearing loss:

  • Blockage of signal transduction of impulses from the outer hair cells in the organ of Corti (mainly in the first row of the basal turn)7
  • Hair cell injury tends to be sporadic in nature and non-continuous7
  • Other sites of injury could include spiral ganglion cells, cochlear neurons and stria vascularis7
  • The stria vascularis provides the main blood supply to the cochlea. Cisplatin may cause ototoxicity indirectly through metabolic derangements that affect this organ2

Cisplatin and aminoglycosides have the same mechanism of hearing loss - the destruction of cochlear sensory hair cells3

Destruction of sensory hair cells typically begins at the base of the cochlea where the high frequency sounds are processed and slowly extends towards the apex where the low frequency sound processing occurs17

Hair cells are unable to regenerate once they are damaged3

Cisplatin Toxicity:

Up to 90% of younger children may suffer moderate to severe hearing deficits

When children are given cumulative doses in excess of 400mg/m2 of cisplatin, 25% of those children will have severe hearing deficits as a long term side effect5

Approximately 50% of children treated with cisplatin-based regimens reportedly develop some degree of permanent hearing loss5

Patients who have therapy at a younger age seem to be more susceptible25


Key Factors

Contributory Factors

Increased risk factors for Cisplatin toxicity:

CNS neoplasm4


Cumulative cisplatin dose of 360mg/m2 or more4


High dose cisplatin (such as 40mg/m2 per day for 5 days)


Cisplatin administered after cranial/ear radiation4


Radiation involving ear of 30Gy or more4


Carboplatin condition for HCT4

Under age of 4 at treatment4


Combination  with ototoxic drugs4


Medical conditions such as:


  • chronic otitis
  • cerumen impaction
  • renal dysfunction4



Mechanism of hearing loss:

  • Little is known about the way Carboplatin induces hearing loss, though it is suspected that it mainly damages the inner hair cells of the cochlea14

Carboplatin Toxicity:

Carboplatin has less auditory toxicity compared to cisplatin, but still may cause or exacerbate high-frequency hearing loss particularly when given in high doses2,23

Carboplatin at cumulative doses greater than 2000mg/m2 can possibly cause minor hearing loss, therefore the risk for severe hearing loss in pediatric patients is relatively low23

The risk of hearing loss mainly increases when this drug is combined with cisplatin therapy23 

  • Perhaps cisplatin makes hair cells more susceptible to subsequent damage or carboplatin causes subclinical damage that only manifests itself when both agents are given23

Age, sex, race, diagnosis does not seem to affect the severity of carboplatin induced hearing loss23



Ifosfamide may exacerbate cisplatin-related hearing loss2

Data regarding Ifosfamide's ototoxicity is still unclear2


Other Drugs:

Loop diuretics and aminoglycosides can cause hearing loss:

Loop diuretics are thought to cause hearing loss secondary to fluid and electrolyte balance changes within the inner ear. This leads to tissue edema within the cochlea and decreased endocochlear potential.  This type of hearing loss is usually transient18

Co-administration of loop diuretics and platinum chemotherapy or aminoglycosides can increase the likelihood of permanent auditory damage19


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