title: Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom.
authors.forename: Penelope R
authors.initials: PR
authors.lastname: Brock
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Knight
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.forename: Kathleen C M
authors.initials: KC
authors.lastname: Campbell
authors.forename: Peter S
authors.initials: PS
authors.lastname: Steyger
authors.forename: Brian W
authors.initials: BW
authors.lastname: Blakley
authors.forename: Shahrad R
authors.initials: SR
authors.lastname: Rassekh
authors.forename: Kay W
authors.initials: KW
authors.lastname: Chang
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Fligor
authors.forename: Kaukab
authors.initials: K
authors.lastname: Rajput
authors.forename: Michael
authors.initials: M
authors.lastname: Sullivan
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D011446:Prospective Studies
chemical_list: D009944:Organoplatinum Compounds