-
Supportive Care in Cancer : Official... Oct 2023Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss.... (Review)
Review
PURPOSE
Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies.
METHODS
We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy."
RESULTS
A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively.
CONCLUSION
We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Melanoma; Hearing Loss; Retrospective Studies
PubMed: 37819422
DOI: 10.1007/s00520-023-08083-w -
Clinical Otolaryngology : Official... Jan 2024Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity... (Review)
Review
OBJECTIVES
Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.
METHODS
Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.
RESULTS
Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.
CONCLUSIONS
Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Topics: Adult; Humans; Cisplatin; Antineoplastic Agents; Carboplatin; Ototoxicity; Hearing Loss; Neoplasms; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 37818931
DOI: 10.1111/coa.14106 -
Ear and HearingChronic substance misuse is an ongoing and significant public health concern. Among a myriad of health complications that can occur, substance misuse potentially causes...
BACKGROUND
Chronic substance misuse is an ongoing and significant public health concern. Among a myriad of health complications that can occur, substance misuse potentially causes ototoxic effects. Case reports, retrospective chart data, and a few cohort studies suggest that certain prescription opioids and illicit drugs can have either temporary or permanent effects on auditory and/or vestibular function. Given the steady rise of people with a substance-use disorder (SUD), it is of growing importance that audiologists and otolaryngologists have an insight into the potential ototoxic effects of substance misuse.
OBJECTIVES
A systematic review was conducted to (1) synthesize the literature on the illicit drugs, prescription opioids, and alcohol misuse on the auditory and vestibular systems, (2) highlight common hearing and vestibular impairments for each substance class, and (3) discuss the limitations of the literature, the potential mechanisms, and clinical implications for clinicians who may encounter patients with hearing or vestibular loss related to substance misuse, and describe opportunities for further study.
DESIGN
Systematic searches were performed via PubMed, Scopus, and Google Scholar, and the final updated search was conducted through March 30, 2022. Inclusion criteria included peer-reviewed articles, regardless of study design, from inception until the present that included adults with chronic substance misuse and hearing and/or vestibular complaints. Articles that focused on the acute effects of substances in healthy people, ototoxicity from already known ototoxic medications, the relationship between hearing loss and development of a SUD, articles not available in English, animal work, and duplicates were excluded. Information on the population (adults), outcomes (hearing and/or vestibular data results), and study design (e.g., case report, cohort) were extracted. A meta-analysis could not be performed because more than 60% of the studies were single-case reports or small cohort.
RESULTS
The full text of 67 studies that met the eligibility criteria were selected for the review. Overall, 21 studies reported associations between HL/VL related to illicit drug misuse, 28 studies reported HL/VL from prescription opioids, and 20 studies reported HL/VL related to chronic alcohol misuse (2 studies spanned more than one category). Synthesis of the findings suggested that the misuse and/or overdose of amphetamines and cocaine was associated with sudden, bilateral, and temporary HL, whereas HL from the combination of a stimulant and an opioid often presented with greater HL in the mid-frequency range. Reports of temporary vertigo or imbalance were mainly associated with illicit drugs. HL associated with misuse of prescription opioids was typically sudden or rapidly progressive, bilateral, moderately severe to profound, and in almost all cases permanent. The misuse of prescription opioids occasionally resulted in peripheral VL, especially when the opioid misuse was long term. Chronic alcohol misuse tended to associate with high-frequency sudden or progressive sensorineural hearing loss, or retrocochlear dysfunction, and a high occurrence of central vestibular dysfunction and imbalance.
CONCLUSIONS
Overall, chronic substance misuse associates with potential ototoxic effects, resulting in temporary or permanent hearing and/or vestibular dysfunction. However, there are notable limitations to the evidence from the extant literature including a lack of objective test measures used to describe hearing or vestibular effects associated with substance misuse, small study sample sizes, reliance on case studies, lack of controlling for confounders related to health, age, sex, and other substance-use factors. Future large-scale studies with prospective study designs are needed to further ascertain the role and risk factors of substance misuse on auditory and vestibular function and to further clinical management practices.
Topics: Adult; Humans; Retrospective Studies; Prospective Studies; Alcoholism; Substance-Related Disorders; Analgesics, Opioid; Illicit Drugs
PubMed: 37784231
DOI: 10.1097/AUD.0000000000001425 -
Therapeutic Drug Monitoring Dec 2023Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic...
BACKGROUND
Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.
METHODS
An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.
RESULTS
Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.
CONCLUSIONS
Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Topics: Adult; Humans; Child; Cisplatin; Antineoplastic Agents; Pharmacogenetics; Ototoxicity; Canada; Acylphosphatase
PubMed: 37726872
DOI: 10.1097/FTD.0000000000001113 -
Seizure Oct 2023Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
BACKGROUND
Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
METHODS
A systematic review of animal and human studies was conducted to evaluate the efficacy and safety of bumetanide for neonatal seizures. PubMed, Embase, CINAHL and Cochrane databases were searched in March 2023.
RESULTS
26 animal (rat or mice) studies describing 38 experiments (28 in-vivo and ten in-vitro) and two human studies (one RCT and one open-label dose-finding) were included. The study designs, methods to induce seizures, bumetanide dose, and outcome measures were heterogeneous, with only 4/38 experiments being in animal hypoxia/ischaemia models. Among 38 animal experiments, bumetanide was reported to have antiseizure effects in 21, pro-seizure in six and ineffective in 11. The two human studies (n = 57) did not show the benefits of bumetanide as an add-on agent to phenobarbital in their primary analyses, but one study reported benefit on post-hoc analysis. Overall, hearing impairment was detected in 5/37 surviving infants in the bumetanide group vs. 0/13 in controls. Four of the five infants with hearing impairment had received aminoglycosides concurrently. Other adverse effects reported were diuresis, mild-to-moderate dehydration, hypotension, and electrolyte disturbances. The studies did not report on long-term neurodevelopment. The certainty of the evidence was very low.
CONCLUSION
Animal data suggest that bumetanide has inconsistent effects as an antiseizure medication in neonates. Data from human studies are scarce and raise some concerns regarding ototoxicity when given with aminoglycosides. Well conducted studies in animal models of hypoxic-ischaemic encephalopathy are urgently needed. Future RCTs, if conducted in human neonates, should have an adequate sample size, assess neurodevelopment, minimize using aminoglycosides, be transparent about the potential ototoxicity in the parent information sheet, conduct early hearing tests and have trial-stopping rules that include hearing impairment as an outcome.
Topics: Infant, Newborn; Infant; Humans; Rats; Mice; Animals; Bumetanide; Ototoxicity; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2; Seizures; Epilepsy; Phenobarbital; Infant, Newborn, Diseases; Aminoglycosides; Hearing Loss; Anticonvulsants
PubMed: 37690372
DOI: 10.1016/j.seizure.2023.09.007 -
Current Molecular Medicine Aug 2023Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as...
INTRODUCTION
Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides.
OBJECTIVE
In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs).
METHODS
We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords "aminoglycosides", "pharmacokinetics", "ODD", "MDD", "once daily", "multiple daily", "dosing regimen", "nephrotoxicity", "ototoxicity", "efficacy", "safety", and "toxicity". As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 21 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years.
RESULTS
The most common clinical condition in the included studies was cystic fibrosis.
CONCLUSION
In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.
PubMed: 37533241
DOI: 10.2174/1566524023666230801160452 -
Current Medicinal Chemistry Jul 2023Although cancer treatment with cisplatin is effective, dose-dependent adverse effects such as ototoxicity occurs often, which limits its clinical use. The use of...
INTRODUCTION
Although cancer treatment with cisplatin is effective, dose-dependent adverse effects such as ototoxicity occurs often, which limits its clinical use. The use of resveratrol may alleviate the cisplatin-induced ototoxic effects. This study is aimed to review the potential otoprotective effects of resveratrol against cisplatin-induced ototoxicity.
METHOD
According to the PRISMA guideline, a systematic search was accomplished to identify all relevant scientific papers on "the role of resveratrol against cisplatin-induced ototoxicity" in different electronic databases up to May 2021. Fifty-five articles were screened based on a pre-defined set of inclusion and exclusion criteria. Eight eligible studies were finally included in the current systematic review. The in-vitro findings revealed that cisplatin administration significantly decreased the HEI-OC1 cell viability compared to the untreated cells; however, resveratrol co-treatment (in a dose-dependent manner) could protect HEI-OC1 cells against cisplatin-induced decrease in cell viability.
RESULTS
Furthermore, the in-vivo finding showed a decreased value of DPOAE, and increased values of ABR threshold, ABR-I, ABR-IV, and ABR I-IV interval in cisplatin-treated animals; in contrast, resveratrol co-administration demonstrated an opposite pattern on these parameters.
CONCLUSION
Thus, it can be mentioned that resveratrol co-treatment alleviates cisplatin-induced ototoxicity. Mechanically, resveratrol exerts its otoprotective effects through various mechanisms such as anti-oxidant, anti-apoptosis, and anti-inflammatory.
PubMed: 37491852
DOI: 10.2174/0929867331666230724124013 -
Brazilian Journal of Otorhinolaryngology 2023To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature.
METHODS
Altogether, 154 articles were found in four databases. The PICOS strategy (Population, Intervention, Comparison, and Outcome) was used to define the eligibility criteria. Studies that met the inclusion criteria for the second step were included in a qualitative synthesis. Each study type was analyzed with the CAMARADES quality of assessment's checklist and the SYRCLE RoBS risk of bias.
RESULTS
Seven articles were selected, and four were included in the meta-analysis. It was possible to obtain seven outcomes according to the standard auditory frequencies presented among the studies, considering a minimum of three standard frequencies. The outcomes analyzed were for the frequencies of 1500, 2000, 3000, 4000, 5000, 6000, and 8000 Hz.
CONCLUSION
Melatonin can provide protection against the ototoxic effects of cisplatin and aminoglycosides at 5000 Hz, 6000 Hz, and 8000 Hz, thereby minimizing the reduction in Otoacustic Emissions (OAE) amplitude. The same effect was not observed in the lower frequencies. Despite the limited number of studies that were evaluated, the results appeared consistent in higher frequencies. However, the methodology of the available studies did not meet the necessary methodological rigor that promotes the safe replicability of these studies.
Topics: Animals; Melatonin; Rodentia; Cisplatin
PubMed: 37451174
DOI: 10.1016/j.bjorl.2023.101288 -
Radiation Oncology (London, England) Jun 2023The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have...
BACKGROUND
The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity.
METHODS
A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model.
RESULTS
Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47-0.60; P = 0.73; I = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00-2.07; P = 0.69; I = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment.
CONCLUSION
Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy.
Topics: Adult; Child; Humans; Hearing; Hearing Loss; Ototoxicity; Radiosurgery; Radiotherapy; Radiotherapy, Intensity-Modulated
PubMed: 37270526
DOI: 10.1186/s13014-023-02268-7 -
Current Medicinal Chemistry May 2023Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate...
PURPOSE
Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity. In the present study, we reviewed the protective potentials of alpha-lipoic acid against the cisplatin-mediated ototoxic adverse effects.
METHODS
Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study.
RESULTS
The findings of in-vitro experiments showed that cisplatin treatment significantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes.
CONCLUSION
The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle progression.
PubMed: 37165582
DOI: 10.2174/0929867330666230509162513