Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss.

Abstract

OBJECTIVES:

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.

• Authors: Patrizia Bertolini, Mathilde Lassalle, Guilaine Mercier, Marie Anne Raquin, Giancarlo Izzi, Nadege Corradini, Olivier Hartmann
• Journal: Journal of pediatric hematology/oncology (J Pediatr Hematol Oncol) Vol. 26 Issue 10 Pg. 649-55 (Oct 2004) ISSN: 1077-4114 [Print] United States
• PMID: 15454836 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carboplatin
• Cisplatin

Topics

• Adolescent
• Age Factors
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Audiometry
• Carboplatin (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Cisplatin (administration & dosage, adverse effects)
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Hair Cells, Auditory, Outer (drug effects)
• Hearing Loss, Sensorineural (chemically induced, epidemiology)
• Humans
• Infant
• Male
• Neoplasms (complications, drug therapy)
• Oxidative Stress
• Retrospective Studies