Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma

Musial-Bright, Lindy; Fengler, R.; Henze, Günter; Driever, Pablo Hernáiz

doi:10.1007/s00381-010-1300-1

Cited by 37 publications

(29 citation statements)

References 36 publications

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“…However, statistical analyses did not identify a statistically significant correlation between cumulative platinum dosage and hearing impairment, in contrast to other studies (6)(7)(8)10,(21)(22)(23).…”

Section: Discussioncontrasting

confidence: 98%

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

et al. 2012

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Section: Discussioncontrasting

confidence: 98%

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

et al. 2012

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“…While neurotoxicity and nephrotoxicity can be mitigated by appropriate clinical regimens, ototoxicity seems inevitable and permanent. Ototoxic effects occur in 26–68% of patients treated with cisplatin (Musial-Bright et al, 2011). An increased risk of permanent hearing loss is reported for younger children, larger doses, pre-existing hearing loss and renal disease (Rybak et al, 2007b).…”

Section: Hearing Loss Due To Ototoxicity Is the Results Of Apoptosismentioning

confidence: 99%

“…Effects on the stria vascularis may contribute to the overall pattern of early cisplatin damage but such effects are initially also reversible. On the other hand, cisplatin induces long term, irreversible changes in the cochlear morphology resulting in an irreversible bilateral, sensorineural high frequency loss (Musial-Bright et al, 2011). These cochleotoxic effects of cisplatin have been well described (Estrem et al, 1981; Laurell et al, 1989) and result from a predominant destruction of the outer hair cells of the organ of Corti starting from the basal turn of the cochlea (Alam et al, 2000).…”

Section: Hearing Loss Due To Ototoxicity Is the Results Of Apoptosismentioning

confidence: 99%

Apoptosis in acquired and genetic hearing impairment: The programmed death of the hair cell

Beeck¹,

Schacht²,

Camp³

2011

Hearing Research

129

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Apoptosis is an important physiological process. Normally, a healthy cell maintains a delicate balance between pro- and anti-apoptotic factors, allowing it to live and proliferate. It is thus not surprising that disturbance of this delicate balance may result in disease. It is a well known fact that apoptosis also contributes to several acquired forms of hearing impairment. Noise-induced hearing loss is the result of prolonged exposure to excessive noise, triggering apoptosis in terminally differentiated sensory hair cells. Moreover, hearing loss caused by the use of therapeutic drugs such as aminoglycoside antibiotics and cisplatin potentially may result in the activation of apoptosis in sensory hair cells leading to hearing loss due to the “ototoxicity” of the drugs. Finally, apoptosis is a key contributor to the development of presbycusis, age-related hearing loss. Recently, several mutations in apoptosis genes were identified as the cause of monogenic hearing impairment. These genes are TJP2, DFNA5 and MSRB3. This implies that apoptosis not only contributes to the pathology of acquired forms of hearing impairment, but also to genetic hearing impairment as well. We believe that these genes constitute a new functional class within the hearing loss field. Here, the contribution of apoptosis in the pathology of both acquired and genetic hearing impairment is reviewed.

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“…One of the major side effects, however, is irreversible high frequency hearing loss. The overall reported incidence of cisplatin-induced hearing loss is between 28–68% [2] and the variability is due to different risk factors including method of administration (i.e. intravenous), age of the patient, and presence of concurrent treatment with radiotherapy or additional chemotherapeutic agents [1].…”

Section: Introductionmentioning

confidence: 99%

Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

et al. 2013

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Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.

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Carboplatin and ototoxicity: hearing loss rates among survivors of childhood medulloblastoma

Abstract: The encouraging overall survival and low hearing loss rates in this medulloblastoma patient cohort suggest that protocols containing carboplatin may offer a viable alternative to standard cisplatin protocols and warrant further investigation.

Cited by 37 publications

References 36 publications

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

Apoptosis in acquired and genetic hearing impairment: The programmed death of the hair cell

Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

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