Long-term effects of carboplatin brainstem infusions on hearing thresholds in monkeys

Bradford Jay May, Michael Guarnieri, Benjamin Solomon, Abdul Bachani, George Jallo

Research output: Contribution to journalArticle

Abstract

Objective: To isolate the central auditory neurotoxicity of carboplatin from its well-established ototoxic effects. Design: The "best-case scenario" of targeted drug delivery to brain cancer was simulated by infusing carboplatin directly into the brainstem of cynomolgus monkeys with chronically implanted catheters. Because this manner of drug administration produced low levels of carboplatin in spinal fluid and blood, it was assumed that resulting deficits were dictated by the central auditory neurotoxicity of platinum compounds and not peripheral ototoxic effects. The magnitude of this hearing loss was estimated by comparing the auditory brainstem response thresholds of treated monkeys with results from normal controls. Subjects: Six adult male cynomolgus monkeys (Macaca fascicularis) weighing 4 to 6 kg (3 received carboplatin treatment and 3 served as normal controls). Intervention: Brainstem infusions of carboplatin. Results: The average threshold of carboplatin-treated monkeys was elevated 8.8 dB (SD = 7.3 dB) relative to normal controls 6 months after the termination of drug delivery and increased to 10.7 dB with less variation between subjects (SD = 5.6 dB) 1 year after drug treatment. Although small in magnitude, the hearing loss was statistically significant (P

Original languageEnglish (US)
Pages (from-to)1411-1415
Number of pages5
JournalArchives of Otolaryngology--Head and Neck Surgery
Volume130
Issue number12
DOIs
StatePublished - Dec 2004

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Carboplatin
Hearing
Brain Stem
Haplorhini
Macaca fascicularis
Hearing Loss
Pharmaceutical Preparations
Platinum Compounds
Brain Stem Auditory Evoked Potentials
Brain Neoplasms
Catheters
Therapeutics

ASJC Scopus subject areas

  • Otorhinolaryngology

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Long-term effects of carboplatin brainstem infusions on hearing thresholds in monkeys. / May, Bradford Jay; Guarnieri, Michael; Solomon, Benjamin; Bachani, Abdul; Jallo, George.

In: Archives of Otolaryngology--Head and Neck Surgery, Vol. 130, No. 12, 12.2004, p. 1411-1415.

Research output: Contribution to journalArticle

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