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Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss
- Source :
- The New England journal of medicine, Vol. 378, no.25, p. 2376-2385 (2018), N Engl J Med, New England Journal of Medicine, Vol. 378, No 25 (2018) pp. 2376-2385
- Publication Year :
- 2018
- Publisher :
- Massachusetts Medical Society, 2018.
-
Abstract
- BACKGROUND: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years. RESULTS: A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively. CONCLUSIONS: The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).
- Subjects :
- 0301 basic medicine
Oncology
Hepatoblastoma
Male
medicine.medical_treatment
Sodium thiosulfate
chemistry.chemical_compound
0302 clinical medicine
Single-Blind Method
Child
ddc:618
Medicine (all)
Incidence
Liver Neoplasms
General Medicine
Cisplatin/administration & dosage/adverse effects
Hepatoblastoma/drug therapy/mortality
030220 oncology & carcinogenesis
Child, Preschool
Combination
Drug Therapy, Combination
Female
Thiosulfates/administration & dosage/adverse effects/therapeutic use
medicine.symptom
Liver Neoplasms/drug therapy/mortality
medicine.drug
Glomerular Filtration Rate
Hearing Loss/chemically induced/prevention & control
medicine.medical_specialty
Adolescent
Hearing loss
Thiosulfates
Article
Cisplatin
Doxorubicin
Follow-Up Studies
Hearing Loss
Humans
Infant
Survival Analysis
03 medical and health sciences
Drug Therapy
Ototoxicity
Internal medicine
otorhinolaryngologic diseases
medicine
Preschool
Chemotherapy
business.industry
Doxorubicin/administration & dosage
medicine.disease
digestive system diseases
Carboplatin
030104 developmental biology
chemistry
business
Subjects
Details
- Language :
- English
- ISSN :
- 00284793
- Database :
- OpenAIRE
- Journal :
- The New England journal of medicine, Vol. 378, no.25, p. 2376-2385 (2018), N Engl J Med, New England Journal of Medicine, Vol. 378, No 25 (2018) pp. 2376-2385
- Accession number :
- edsair.doi.dedup.....948bb74e3d22b6d4d0b5bb2934618063