ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Intravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- N-acetylcysteine for the Prevention of Cisplatin-Induced Hearing Loss: A Systematic Review and Meta-analysis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025Pooled it
- Therapeutic Effects of N-Acetylcysteine-Primed, Iron Oxide Nanoparticle-Enhanced Mesenchymal Stem Cell Exosomes in Ototoxicity Hearing Loss.Tissue engineering and regenerative medicine · 2026Article
- Early Detection of Ototoxicity Using Serial Mobile Audiometry, Otoacoustic Emissions Testing, and Inner Ear Biomarker Measurement in Patients Receiving Platinum-Based Chemotherapy Treatment: It is Feasible to Implement in a National Health Service (NHS) Cancer Ambulatory Care Setting.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2026Observational
- Therapeutic Potential of MgHNeuroscience bulletin · 2026Article
- Article
- Oxidative stress and reactive oxygen species in otorhinolaryngological diseases: insights from pathophysiology to targeted antioxidant therapies.Redox report : communications in free radical research · 2025Review
- Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- New Approaches and Strategies for the Repurposing of Iron Chelating/Antioxidant Drugs for Diseases of Free Radical Pathology in Medicine.Antioxidants (Basel, Switzerland) · 2025Review
- Development and Validation of a Novel Prediction Model for Hearing Loss From Cisplatin Chemotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Ferulic Acid Combines with Ascorbic Acid to Target MMP9 to Attenuate Cisplatin-Induced Ototoxicity Through the p38MAPK Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Platinum-induced ototoxicity and hearing impairment in children and adolescents.Drugs in context · 2025Review
- Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy-A State-of-the-Art Review.Antioxidants (Basel, Switzerland) · 2024Review
- Nuciferine Protects Cochlear Hair Cells from Ferroptosis through Inhibiting NCOA4-Mediated Ferritinophagy.Antioxidants (Basel, Switzerland) · 2024Article
- Oseltamivir (Tamiflu), a Commonly Prescribed Antiviral Drug, Mitigates Hearing Loss in Mice.bioRxiv : the preprint server for biology · 2024Article
- Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.Biologics : targets & therapy · 2024Review
- Hearing loss during chemotherapy: prevalence, mechanisms, and protection.American journal of cancer research · 2024Review
- Combinatorial protection of cochlear hair cells: not too little but not too much.Frontiers in cellular neuroscience · 2024Article
- Dabrafenib protects from cisplatin-induced hearing loss in a clinically relevant mouse model.JCI insight · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeCisplatin-induced hearing loss (CIHL) is common and permanent. As compared with earlier otoprotectants, we hypothesized N-acetylcysteine (NAC) offers potential for stronger otoprotection through stimulation of glutathione (GSH) production. This study tested the optimal dose, safety, and efficacy of NAC to prevent CIHL. PATIENTS AND
methodsIn this nonrandomized, controlled phase Ia/Ib trial, children and adolescents newly diagnosed with nonmetastatic, cisplatin-treated tumors received NAC intravenously 4 hours post-cisplatin. The trial performed dose-escalation across three dose levels to establish a safe dose that exceeded the targeted peak serum NAC concentration of 1.5 mmol/L (as identified from preclinical models). Patients with metastatic disease or who were otherwise ineligible were enrolled in an observation-only/control arm. To evaluate efficacy, serial age-appropriate audiology assessments were performed. Integrated biology examined genes involved in GSH metabolism and post-NAC GSH concentrations.
resultsOf 52 patients enrolled, 24 received NAC and 28 were in the control arm. The maximum tolerated dose was not reached; analysis of peak NAC concentration identified 450 mg/kg as the recommended phase II dose (RP2D). Infusion-related reactions were common. No severe adverse events occurred. Compared with the control arm, NAC decreased likelihood of CIHL at the end of cisplatin therapy [OR, 0.13; 95% confidence interval (CI), 0.021-0.847; P = 0.033] and recommendations for hearing intervention at end of study (OR, 0.082; 95% CI, 0.011-0.60; P = 0.014). NAC increased GSH; GSTP1 influenced risk for CIHL and NAC otoprotection.
conclusionsNAC was safe at the RP2D, with strong evidence for efficacy to prevent CIHL, warranting further development as a next-generation otoprotectant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.