Platinum-induced ototoxicity in children

A consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale

Penelope R. Brock, Kristin Knight, David R. Freyer, Kathleen C M Campbell, Peter Steyger, Brian W. Blakley, Shahrad R. Rassekh, Kay W. Chang, Brian J. Fligor, Kaukab Rajput, Michael Sullivan, Edward Neuwelt

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Purpose: The platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important. Patients and Methods: This review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection. Results: Platinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss. Conclusion: Collaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.

Original languageEnglish (US)
Pages (from-to)2408-2417
Number of pages10
JournalJournal of Clinical Oncology
Volume30
Issue number19
DOIs
StatePublished - Jul 1 2012

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Platinum
Consensus
Pediatrics
Hearing Loss
Cisplatin
Carboplatin
Clinical Trials
Research
Sulfhydryl Compounds
DNA Repair
Hearing
Neoplasms
Antioxidants
Nurses
Drug Therapy
Incidence
Therapeutics
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Platinum-induced ototoxicity in children : A consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. / Brock, Penelope R.; Knight, Kristin; Freyer, David R.; Campbell, Kathleen C M; Steyger, Peter; Blakley, Brian W.; Rassekh, Shahrad R.; Chang, Kay W.; Fligor, Brian J.; Rajput, Kaukab; Sullivan, Michael; Neuwelt, Edward.

In: Journal of Clinical Oncology, Vol. 30, No. 19, 01.07.2012, p. 2408-2417.

Research output: Contribution to journalArticle

Brock, Penelope R. ; Knight, Kristin ; Freyer, David R. ; Campbell, Kathleen C M ; Steyger, Peter ; Blakley, Brian W. ; Rassekh, Shahrad R. ; Chang, Kay W. ; Fligor, Brian J. ; Rajput, Kaukab ; Sullivan, Michael ; Neuwelt, Edward. / Platinum-induced ototoxicity in children : A consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 19. pp. 2408-2417.
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AU - Steyger, Peter

AU - Blakley, Brian W.

AU - Rassekh, Shahrad R.

AU - Chang, Kay W.

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AU - Sullivan, Michael

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