The incidence of hearing impairment after successful treatment of neuroblastoma.
BACKGROUND
Platinum compound based chemotherapy has contributed to improved survival rates in neuroblastoma patients. We studied the association of hearing loss with the use of platinum based drugs.


METHODS
Data of children from the two German neuroblastoma study cohorts, NB90 and NB97, were analyzed for the incidence of hearing impairments greater than WHO grade 2. Data from patients surviving more than 1 year after diagnosis without progression or recurrence were used.


RESULTS
Of these 1,170 patients, 146 (12.5 %) had persisting hearing impairments. The incidence was low after localized neuroblastoma INSS stage 1 - 3 with 35/650 (5 %) and stage 4S with 2/113 (2 %), but high in stage 4 disease with 109/405 (27 %). Ototoxicity depended on the cumulative cisplatin dose. For doses of 1 - 200 mg/m (2), 201 - 400 mg/m (2), 401 - 600 mg/m (2) and 601 - 800 mg/m (2) we found hearing impairments in 5/39 (12 %), 28/221 (13 %), 61/230 (26 %) and 50/225 (22 %) patients, respectively. The incidence of hearing impairment was not age dependent. In stage 4 patients, there was an additional effect of high dosed carboplatin. 65/188 (40 %) patients developed hearing impairments after carboplatin containing (1,500 mg/m (2)) high dose chemotherapy with autologous stem cell reinfusion compared to only 33/217 (15 %) in patients receiving platinum free maintenance chemotherapy. Substitution of cisplatin (40 mg/m (2) x d, d 1 - 4, 96 h infusion) with carboplatin (100 mg/m (2) x d, d 1 - 4, 1 - 2 h infusion) due to otoxicity during induction chemotherapy did not reduce event free survival.


CONCLUSIONS
One fourth of high risk neuroblastoma survivors suffer from treatment induced hearing impairments. The substitution of cisplatin with carboplatin was not associated with an increased rate of tumor recurrences.
Simon
T
T
Children's Hospital, Köln,Germany. thorsten.simon@medizin.uni-koeln.de
Hero
B
B
Dupuis
W
W
Selle
B
B
Berthold
F
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D033581:Stem Cell Transplantation
D016190:Carboplatin; D002945:Cisplatin