Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma.
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.
Kushner
Brian H
BH
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. kushnerb@mskcc.org
Budnick
Amy
A
Kramer
Kim
K
Modak
Shakeel
S
Cheung
Nai-Kong V
NK
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D005047:Etoposide; D002945:Cisplatin