Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma

Abstract

Background: The young age of neuroblastoma patients makes them especially prone to the ototoxic effects of widely used treatments that feature aggressive use of platinum compounds. We present data defining the extent of the problem in a large series of neuroblastoma patients whose induction included high-dose cisplatin/etoposide (HD-P/E) as used in both the Memorial Sloan-Kettering Cancer Center N7 regimen and the Children's Oncology Group A3973 study.

Methods: N7/A3973 patients were divided into 3 groups: Group 1 had hearing tested after induction, that included 2 cycles of HD-P/E (cumulative cisplatin = 400 mg/m(2)); Group 2 had hearing tested after induction, that included 3 cycles of HD-P/E (cumulative cisplatin = 600 mg/m(2)); and Group 3 had hearing tested following carboplatin-containing myeloablative therapy administered after induction, that included 2 cycles of HD-P/E. Ototoxicity was scored by the Brock method.

Results: All 3 groups had similar clinical characteristics, including median age at diagnosis of about 3 years. Little or no hearing loss in the speech range (Grade 0/1) was documented in 21 (32%) of the 65 Group 1 patients, 5 (10%) of the 50 Group 2 patients, and 9 (15.5%) of the 58 Group 3 patients. Severe (Grade 3/4) deficits affected 25% of Group 1, 54% of Group 2, and 50% of Group 3 patients. Patients < 5 years at diagnosis had greater ototoxicity than older patients had, with adolescents/adults being the least affected. Findings were stable in repeated assessments over 2 or more years.

Conclusions: Ototoxicity is a serious and pervasive problem in this patient population. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed.