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Updated: Jun 27, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Ototoxicity in children treated for osteosarcoma
Matthew J Lewis1, Steven G DuBois, Brian Fligor
1Department of Pediatric Hematology/Oncology, Dana Farber-Cancer Institute/Children's Hospital, Boston, Massachusetts 02115, USA.
Background:
Cisplatin is an effective agent against osteosarcoma. Ototoxicity from osteosarcoma treatment protocols has not been well defined. The aim of this study was to determine the incidence and risk factors for hearing loss in children treated for osteosarcoma.
Procedure:
Eligible patients had osteosarcoma diagnosed and treated at the Dana-Farber Cancer Institute/Children's Hospital Boston from January 1, 1995 to December 12, 2004, were 3-18 years of age at diagnosis, and had a normal audiogram prior to the start of chemotherapy. Patients received cisplatin according to the standard practice or current open protocol. Patients who developed hearing loss during treatment had cisplatin held on an individualized basis. Hearing function was evaluated prior to the start of therapy, before each cycle, and off-therapy. Fisher's exact test and logistic regression models were used to identify univariate and independent predictors of hearing loss, respectively.
Results:
Seven out of nine patients (78%) who received cisplatin 120 mg/m(2)/day on 1 day developed hearing loss compared to 8/27 (30%) who received 60 mg/m(2)/day for 2 days (P = 0.019). Logistic regression showed that age, cumulative cisplatin dose, and administration of cisplatin 120 mg/m(2)/day were independent predictors of hearing loss. Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence (30%) of any hearing loss and a very low incidence (4%) of educationally significant hearing loss.
Conclusions:
Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence of significant hearing loss. These results suggest that cisplatin as 120 mg/m(2)/day be avoided due to an unacceptable incidence of hearing loss.
Insights
A modified cisplatin dosage (60 mg/m(2)/day for 2 days) significantly reduced hearing loss in pediatric osteosarcoma patients. This lower dose regimen is recommended over the higher single-day dose to mitigate ototoxicity risks.
Area of Science:
- Pediatric Oncology
- Ototoxicity Research
- Chemotherapy Side Effects
Background:
- Cisplatin is a vital chemotherapy for osteosarcoma.
- Ototoxicity risks associated with cisplatin in pediatric osteosarcoma are not well-defined.
- This study aimed to identify hearing loss incidence and risk factors in children undergoing osteosarcoma treatment.
Purpose of the Study:
- To determine the incidence of hearing loss in children treated for osteosarcoma.
- To identify risk factors associated with cisplatin-induced ototoxicity.
- To compare hearing loss rates between different cisplatin dosing regimens.
Main Methods:
- Retrospective analysis of pediatric osteosarcoma patients (ages 3-18) treated between 1995-2004.
- Audiograms were performed before, during, and after chemotherapy.
- Fisher's exact test and logistic regression analyzed hearing loss predictors.
Main Results:
- 78% of patients receiving high-dose cisplatin (120 mg/m(2)/day) experienced hearing loss versus 30% with the modified dose (60 mg/m(2)/day for 2 days).
- Independent predictors of hearing loss included age, cumulative cisplatin dose, and the high-dose regimen.
- The modified 2-day regimen showed a 30% overall hearing loss rate and only 4% educationally significant hearing loss.
Conclusions:
- Administering cisplatin at 60 mg/m(2)/day for 2 days resulted in a low incidence of significant hearing loss.
- The high-dose cisplatin regimen (120 mg/m(2)/day) should be avoided due to its high ototoxicity rate.
- This modified dosing strategy can help preserve hearing in pediatric osteosarcoma patients.
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