Hearing loss and platinum-based therapy

Platinum-related sensorineural hearing loss develops as an acute toxicity that is generally irreversible and bilateral.[9]

The prevalence of hearing loss has varied widely per series and is based on platinum treatment (e.g., platinum type, dose, infusion duration); host factors (e.g., age, genetic susceptibility, renal function); receipt of additional ototoxic therapy (cranial radiation therapy, aminoglycosides, loop diuretics), and the grading criteria used to report prevalence and severity of hearing loss.[8-10]

Hearing loss manifests initially in the high frequencies and progresses to the speech frequencies with increasing cumulative exposure.[9]

Cisplatin-induced hearing loss involving the speech frequencies (500–2,000 Hz) usually occurs with cumulative doses that exceed 400 mg/m2 in pediatric patients.[11,12]

Prolonging the duration of infusion or splitting the dose has been reported to reduce the risk of significant hearing loss.[13]

In two randomized trials (Children's Oncology Group ACCL0431 [NCT00716976] and International Childhood Liver Tumour Strategy Group SIOPEL-6 [NCT00652132]), sodium thiosulfate demonstrated efficacy in preventing cisplatin-induced hearing loss.[14,15] The SIOPEL-6 trial compared cisplatin alone with cisplatin plus delayed administration of sodium thiosulfate (sodium thiosulfate administered 6 hours after cisplatin) resulted in a 48% lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma. Sodium thiosulfate treatment did not jeopardize the overall survival or event-free survival.[15] These trials led to regulatory approval of sodium thiosulfate for prevention of cisplatin-induced hearing loss. However, each trial used a different hearing end point. In 2010, the SIOP-Boston ototoxicity scale was developed to overcome key limitations of the available scales, and it is central to harmonizing hearing end points. Using the SIOP scale, hearing outcomes from the ACCL0431 trial were re-evaluated. This analysis showed that children treated with sodium thiosulfate were approximately 90% less likely to develop higher than grade 2 cisplatin-induced hearing loss during the trial period or at the end of cisplatin therapy, compared with the observation group.[16]

Otologic toxic effects after platinum chemotherapy have been reported to worsen years after completion of therapy.[17]

Radiation therapy to the posterior fossa inclusive of the eighth cranial nerve (suggestive of damage to the cochlea at the end of therapy) increases the risk of late-onset hearing loss in survivors treated with cisplatin.[18]

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations:

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations:

In a cross-sectional, multicenter analysis that included 451 Dutch childhood cancer survivors who received platinum agents but not cranial radiation therapy, the incidence of ototoxicity (defined as Münster grade >2b [>20 dB at ≥4–8kHz]) associated with the use of carboplatin alone (n = 112) was 17%.[8]

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations:

A single study of otologic toxic effects after non-HSCT dosing of carboplatin for retinoblastoma reported that 8 of 175 children developed hearing loss. For seven of the eight children, the onset of the otologic toxic effects was delayed a median of 3.7 years.[20]

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations:

Another study that evaluated audiological outcomes among 60 retinoblastoma survivors treated with nonmyeloablative systemic carboplatin and vincristine estimated a cumulative incidence of hearing loss of 20.3% at 10 years.[21]

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations: › Another study that evaluated audiological outcomes among 60 retinoblastoma survivors treated with nonmyeloablative systemic carboplatin and vincristine estimated a cumulative incidence of hearing loss of 20.3% at 10 years.[21]

Among the ten patients (17%) who developed sustained grade 3 or grade 4 hearing loss, nine were younger than 6 months at the start of chemotherapy.

Carboplatin used in conventional (nonmyeloablative) dosing is typically not ototoxic.[19] However, delayed-onset hearing loss has been reported in the following populations: › Another study that evaluated audiological outcomes among 60 retinoblastoma survivors treated with nonmyeloablative systemic carboplatin and vincristine estimated a cumulative incidence of hearing loss of 20.3% at 10 years.[21]

Younger age at the start of treatment was the only significant predictor of hearing loss. The cumulative incidence of hearing loss was 39% for patients younger than 6 months versus only 8.3% for patients aged 6 months and older.

The use of a carboplatin conditioning regimen for HSCT, particularly in combination with previous carboplatin or cisplatin therapy, may cause significant otologic toxic effects.[11,12]

The use of a carboplatin conditioning regimen for HSCT, particularly in combination with previous carboplatin or cisplatin therapy, may cause significant otologic toxic effects.[11,12]

One series evaluated 115 patients with recurrent or refractory germ cell tumors (median age, 32 years) who had received first-line cisplatin-based chemotherapy. The study reported hearing outcomes for adolescents and young adults treated with three cycles of high-dose carboplatin therapy. Of the 106 patients with normal hearing or mild hearing loss before high-dose carboplatin therapy, 70 (66%) developed moderate-to-profound hearing loss in the speech frequencies after high-dose carboplatin therapy. Twenty-five patients (22%) were recommended for hearing aids after high-dose carboplatin therapy. Patients with moderate-to-profound hearing loss isolated to higher frequencies before high-dose carboplatin therapy were more likely to develop moderate-to-profound hearing loss in the speech frequencies after therapy and be recommended for hearing aids.[22]