Case report
Recovery from cisplatin-induced ototoxicity: A case report and review

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Summary

We present a pediatric case report of cisplatin-induced ototoxicity with subsequent recovery. The patient experienced tinnitus and fluctuating mild high-frequency sensorineural hearing loss (SNHL) with a concomitant decrease in distortion product otoacoustic emissions (DPOAE). There was recovery of hearing loss and return of DPOAE at 1 year after completion of cisplatin therapy. Reports of recovery from cisplatin-induced ototoxicity in humans are limited in the literature, especially in the pediatric population. A review of cisplatin ototoxicity and mechanisms of recovery are discussed, with an emphasis on the particular chemotherapy regimen and dosing schedule in this case, given at 4–11 week intervals.

Introduction

Cisplatin is widely used for the treatment of osteosarcoma, hepatoblastoma, neuroblastoma, germ cell tumors, head and neck cancers and some central nervous system tumors. Multiple toxicities have been reported including, peripheral neuropathy, nephrotoxicity, nausea/vomiting and ototoxicity. Ototoxicity has been generally characterized as progressive, irreversible, bilateral hearing loss with tinnitus [1]. Ototoxic hearing loss has been described as high frequency, sensorineural with progression to lower frequencies. The incidence of hearing loss has been reported to be 42% of those receiving higher doses (70–85 mg/m2, cumulative dose of 420 mg) with critical cumulative doses described as low as 200 mg and up to 400 or 600 mg [2], [3].

Children have been reported to be more susceptible to ototoxicity, especially with higher dose regimens (200–400 mg/m2) [4], [5]. High-frequency loss is associated with loss of consonant sounds or fricatives [6]. Hearing loss in children can lead to speech and language delay, as well as academic difficulties. As more children are surviving their childhood neoplasms, hearing preservation is imperative as well as early identification of hearing loss for appropriate management [7]. It has been recommended that close follow-up with pure tone audiometry be performed so alterations in chemotherapy doses can be made to preserve hearing. It has also been proposed that monitoring DPOAE is a more sensitive means of monitoring ototoxicity, with earlier detection than audiometry. Evidence shows that the cumulative cisplatin dose as well as method of infusion play roles in extent of ototoxicity [8]. In this case we show that dosing schedule also plays a significant role in ototoxicity. We present a case of ototoxicity that presented with tinnitus, fluctuating high-frequency hearing loss and concomitant fluctuating DPOAE with nearly complete recovery of both pure tone thresholds and DPOAE at 1 year post treatment.

Section snippets

Case report

The patient, a 16-year-old male, was referred to Lucile Packard Children's Hospital after noting right shoulder pain while playing basketball. After several weeks of continued pain and swelling, an AP X-ray of the right humerus showed a large soft tissue mass. An MRI confirmed a large primary bone tumor, 7 cm in the long axis, and 6.2 cm in diameter. There was no evidence of metastatic disease on further workup. An open biopsy confirmed the diagnosis of osteosarcoma.

The patient then began

Discussion

We present a case of a 16-year-old patient treated with cisplatin for osteosarcoma who reported bilateral tinnitus immediately following cisplatin infusion, followed by bilateral fluctuating high-frequency sensorineural hearing loss (HFSNHL) with reduced/absent DPOAE. He received four doses of cisplatin for a cumulative dose of 854 mg over 23 weeks, given in 4–11 week intervals. The patient demonstrated a pattern of tinnitus, hearing loss, and reduced/absent DPOAE that showed recovery over the

Cisplatin ototoxicity

Platinum compounds were first recognized by Rosenburg and Calalieri in 1964 for their therapeutic potential, though clinical trials of cisplatin as a chemotherapeutic agent did not begin until 1971. Final approval for its use in human cancer therapy was achieved in 1978. Ototoxicity was recognized early in case reports in 1972, and cisplatin has been identified as the most ototoxic of all platinum compounds [9]. Predisposing factors for ototoxicity reported are dose, duration, mode of

Pathophysiology of cisplatin ototoxicity: early damage to the stria vascularis progresses to OHC death

Several studies have shown that damage to the stria vascularis precedes OHC loss in cisplatin ototoxicity [19], [20], [21]. It has been proposed that damage to the marginal cells of the stria vascularis secondarily causes damage to the OHC [22], [23]. In a study by Miyasha et al., photochemically induced damage to the cochlea with Rose Bengal dye and green light irradiation resulted in marginal cell extrusion and rupture, followed by OHC damage 12 or more hours after strial insult as seen by

Recovery of ototoxicity

Why cisplatin accumulates in strial marginal cells in not clear, though it is hypothesized that cisplatin is actively transported into these cells and trapped [21]. The exact mechanism of strial damage leading to outer hair cell damage and death is also unclear. However, the progression from strial damage to OHC loss may be a graduated process that may provide a mechanism to explain the reversibility of hearing loss that has been described in animal models as well as few human case reports

Monitoring for ototoxicity: pure tone audiometry, ABR, DPOAE

Pure tone behavioral audiometry remains the standard means to monitor for ototoxicity and hearing loss. Since cisplatin ototoxicity preferentially affects the basal end of the cochlea, high-frequency audiometry is a more sensitive method of detecting early ototoxicity [34], [35]. The pediatric oncology population is frequently difficult to test behaviorally, and therefore auditory brainstem response (ABR) and DPOAE are sometimes useful objective studies that can be obtained. Tone burst

Conclusions

In this case report, we present a pediatric case of recovery of mild high-frequency sensorineural hearing loss after cisplatin ototoxicity. The patient reported tinnitus immediately following the initiation of cisplatin therapy, followed by a dosing schedule of 4–11 week intervals between doses, allowing for appropriate time for reparative processes in the cochlea. In this case, DPOAE did not provide earlier detection of hearing loss, however correlated very closely to audiometric threshold

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