Ototoxicity of carboplatin delivered locally in a monkey brainstem

J. P. Carey, Timothy Cooper, G. I. Jallo, B. S. Carson, M. Guarnieri

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 μl/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.

Original languageEnglish (US)
Pages (from-to)443-449
Number of pages7
JournalInternational journal of toxicology
Volume24
Issue number6
DOIs
StatePublished - Nov 1 2005

Fingerprint

Carboplatin
Vestibular Hair Cells
Brain Stem
Haplorhini
Cells
Cerebrospinal fluid
Animals
Platinum
Maximum Tolerated Dose
Microscopic examination
Drug infusion
Pharmaceutical Preparations
Cerebrospinal Fluid
Cell Count
Histology
Chemotherapy
Neurology
Central Nervous System Neoplasms
Drug delivery
Macaca fascicularis

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Carey, J. P., Cooper, T., Jallo, G. I., Carson, B. S., & Guarnieri, M. (2005). Ototoxicity of carboplatin delivered locally in a monkey brainstem. International journal of toxicology, 24(6), 443-449. https://doi.org/10.1080/10915810500368951
Carey, J. P. ; Cooper, Timothy ; Jallo, G. I. ; Carson, B. S. ; Guarnieri, M. / Ototoxicity of carboplatin delivered locally in a monkey brainstem. In: International journal of toxicology. 2005 ; Vol. 24, No. 6. pp. 443-449.
@article{ad0c460c49754cb1b4e2078e4674e812,
title = "Ototoxicity of carboplatin delivered locally in a monkey brainstem",
abstract = "Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 μl/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.",
author = "Carey, {J. P.} and Timothy Cooper and Jallo, {G. I.} and Carson, {B. S.} and M. Guarnieri",
year = "2005",
month = "11",
day = "1",
doi = "10.1080/10915810500368951",
language = "English (US)",
volume = "24",
pages = "443--449",
journal = "International Journal of Toxicology",
issn = "1091-5818",
publisher = "SAGE Publications Inc.",
number = "6",

}

Carey, JP, Cooper, T, Jallo, GI, Carson, BS & Guarnieri, M 2005, 'Ototoxicity of carboplatin delivered locally in a monkey brainstem', International journal of toxicology, vol. 24, no. 6, pp. 443-449. https://doi.org/10.1080/10915810500368951

Ototoxicity of carboplatin delivered locally in a monkey brainstem. / Carey, J. P.; Cooper, Timothy; Jallo, G. I.; Carson, B. S.; Guarnieri, M.

In: International journal of toxicology, Vol. 24, No. 6, 01.11.2005, p. 443-449.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ototoxicity of carboplatin delivered locally in a monkey brainstem

AU - Carey, J. P.

AU - Cooper, Timothy

AU - Jallo, G. I.

AU - Carson, B. S.

AU - Guarnieri, M.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 μl/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.

AB - Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 μl/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.

UR - http://www.scopus.com/inward/record.url?scp=30344454369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30344454369&partnerID=8YFLogxK

U2 - 10.1080/10915810500368951

DO - 10.1080/10915810500368951

M3 - Article

C2 - 16393937

AN - SCOPUS:30344454369

VL - 24

SP - 443

EP - 449

JO - International Journal of Toxicology

JF - International Journal of Toxicology

SN - 1091-5818

IS - 6

ER -