Early Changes in Auditory Function As a Result of Platinum Chemotherapy: Use of Extended High-Frequency Audiometry and Evoked Distortion Product Otoacoustic Emissions

Knight, Keith; Kraemer, Dale F.; Winter, Christiane; Neuwelt, Edward A.

doi:10.1200/jco.2006.07.9723

Cited by 207 publications

(208 citation statements)

References 16 publications

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“…As reviewed by Rybak (2005), hearing loss occurs in 30 to 100% of patients treated with cisplatin. Hearing loss may occur during treatment (Knight et al, 2005(Knight et al, , 2007Orgel et al, 2012) or after discontinuation of chemotherapy (Al-Khatib et al, 2010;Kolinsky et al, 2010). Furthermore, patients treated with cisplatin exhibit severe difficulty in word recognition (Einarsson et al, 2011), suggesting a central component in their hearing loss.…”

Section: Introductionmentioning

confidence: 99%

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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Cisplatin is a platinum-based chemotherapeutic agent widely used for the treatment of various types of cancer. Patients undergoing cisplatin treatment often suffer from a condition known as "chemobrain", ototoxicity, peripheral neuropathy, weight loss, nausea, vomiting, nephrotoxicity, seizures, hearing loss and tinnitus.D-Methionine (D-Met), a sulfur-containing nucleophilic antioxidant, has been shown to prevent cisplatininduced side effects in animals without antitumor interference. In this study, we have used an in vitro model of cortical networks (CNs), enriched in auditory cortex cells; to quantify cisplatin neurotoxicity and the protective effects of D-Met. Dissociated neurons from auditory cortices of mouse embryos were grown on microelectrode arrays with 64 transparent indium-tin oxide electrodes, which enabled continuous optical and electrophysiological monitoring of network neurons. Cisplatin at 0.10-0.25 mM induced up to a 200% increase in spontaneous spiking activity, while concentrations at or above 0.5 mM caused irreversible loss of neuronal activity, accompanied by cell death. Pretreatment with D-Met, at a concentration of 1.0 mM, prevented the cisplatin-induced excitation at 0.10-0.25 mM, caused sustained excitation without occurrence of cell death at 0.5 mM, and delayed cell death at 0.75 mM cisplatin. L-Methionine, the optical isomer, showed lower potency and less efficacy than D-Met, was less protective against 0.1 mM cisplatin, and proved ineffective at a concentration of 0.5 mM cisplatin. Pre-exposure time of D-Met was associated with the protective effects at 0.1 and 0.5 mM cisplatin, with longer pre-exposure times exhibiting better protection. This study quantifies as a function of concentration and time that D-Met protects central nervous system tissue from acute cisplatin toxicity.

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Section: Introductionmentioning

confidence: 99%

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Gopal

Shrestha

et al. 2012

Neurotoxicology and Teratology

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“…One patient experienced subclinical, unilateral ototoxicity on pure tone audiograms that did not revert after 18 months of follow-up. In addition to pure tone audiometry, we also studied DPOAEs that are known to represent the contractile amplifier of the outer hair cells (18). Low or absent DPOAEs are associated with hearing loss on audiograms yet can also be associated with normal audiograms.…”

Section: Discussionmentioning

confidence: 99%

“…DPOAE results were based on a shift of 6 dB or more (17). DPOAEs are known to represent the contractile amplifier function of cochlear outer hair cell and may represent an earlier and more sensitive indicator of early ototoxicity (18).…”

Section: Audiometrymentioning

confidence: 99%

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Sinicrope

Broaddus

Joshi

et al. 2011

Cancer Prevention Research

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Patients with Barrett's esophagus (BE) and dysplasia are candidates for chemopreventive strategies to reduce cancer risk. We determined the effects of difluoromethylornithine (DMFO) on mucosal polyamines, gene expression, and histopathology in BE. Ten patients with BE and low-grade dysplasia participated in a single-arm study of DFMO (0.5 g/m 2 /d) given continuously for 6 months. Esophagoscopy with biopsies was conducted at baseline, 3, 6, and 12 months. Dysplasia was graded by a gastrointestinal pathologist. Audiology was assessed (at baseline and at 6 months). Mucosal polyamines were measured by high-performance liquid chromatography. Microarray-based gene expression was analyzed using a cDNA two-color chip. DFMO suppressed levels of the polyamines putrescine (P ¼ 0.02) and spermidine (P ¼ 0.02) and the spermidine/spermine ratio (P < 0.01) in dysplastic BE (6 months vs. baseline) that persisted at 6 months following drug cessation. Among the top 25 modulated genes, we found those regulating p53-mediated cell signaling (RPL11), cell-cycle regulation (cyclin E2), and cell adhesion and invasion (Plexin1). DFMO downregulated Kr€ uppellike factor 5 (KLF5), a transcription factor promoting cell proliferation, and suppressed RFC5 whose protein interacts with proliferating cell nuclear antigen. Histopathology showed regression of dysplasia (n ¼ 1), stable disease (n ¼ 8), and progression to high-grade dysplasia (n ¼ 1). Polyamines were suppressed in the responder to a greater extent than in stable cases. DFMO was well tolerated, and one patient had subclinical, unilateral ototoxicity. DFMO suppressed mucosal polyamines and modulated genes that may be mechanistically related to its chemopreventive effect. Further study of DFMO for the chemoprevention of esophageal cancer in BE patients is warranted.

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“…Conventional audiograms will fail to detect the early signs of hearing loss because they typically do not assay frequencies above 4,000 Hz. This is a special concern for children, because diminished hearing predicts diminished school performance (Knight et al, 2007).…”

Section: Sensory Endpointsmentioning

confidence: 99%

Chemobrain: A translational challenge for neurotoxicology

Weiss

2008

NeuroToxicology

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Neurotoxicity is a frequent accompaniment of cancer chemotherapy, and held by many oncologists to be the major dose-limiting side effect. It appears in many forms, but attracted attention during the past decade primarily because of complaints by patients of impaired cognitive function they have labeled as "chemobrain". Neuropsychological testing confirmed the validity of these complaints and has generated a substantial literature examining different aspects of cognitive impairment in various clinical populations undergoing a variety of treatments. Cognitive impairment is far from the only manifestation of neurotoxicity induced by chemotherapy, however. It alters sensory function and motor function as well. A critical need for patients is a suite of methods that will enable clinicians to trace the onset and progression of neurotoxicity so as to guide and balance decisions about the course of chemotherapy. This commentary describes some of the potential methods and encourages neurotoxicologists to enlist their unique skills in the service of these needs.

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Early Changes in Auditory Function As a Result of Platinum Chemotherapy: Use of Extended High-Frequency Audiometry and Evoked Distortion Product Otoacoustic Emissions

Abstract: EHF audiometry and DPOAEs have the potential to reveal earlier changes in auditory function than conventional frequency audiometry during platinum chemotherapy in children.

Cited by 207 publications

References 16 publications

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks

Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia

Chemobrain: A translational challenge for neurotoxicology

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