Platinum Compound-Related Ototoxicity in Children: Long-Term Follow-Up Reveals Continuous Worsening of Hearing Loss.
OBJECTIVE
The purpose of this study was to evaluate the severity of hearing loss after cisplatin and/or carboplatin treatment in young children and to analyze its evolution and its relation to different therapy schedules.


METHODS
One hundred twenty patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's grading scale, was revealed with pure tone audiometry and behavioral techniques.


RESULTS
Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above was observed in 37% of patients treated with cisplatin and 43% of patients treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400 mg/m. No improvement was observed with time; on the contrary, worsening or progression of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of follow-up.


CONCLUSIONS
Children treated with cisplatin at cumulative doses approaching 400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin, at a standard dose, does not appear to be a significant risk factor for ototoxicity even in patients who have already been treated with cisplatin.
From *Pediatric Hematology/Oncology, Azienda Ospedaliera-Universitaria di Parma, Parma, Italy; †Biostatistics and Epidemiology Service, Institut Gustave-Roussy, Villejuif, France; ‡Groupe Recherche Audiologie Medicale, Paris, France; and §Department of Pediatrics, Institut Gustave-Roussy, Villejuif, France.
Patrizia
P
Bertolini
Mathilde
M
Lassalle
Guilaine
G
Mercier
Marie Anne
MA
Raquin
Giancarlo
G
Izzi
Nadege
N
Corradini
Olivier
O
Hartmann