title: Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma.
abstract: OBJECTIVE
  To determine the role of amifostine as a protectant against cisplatin-induced ototoxicity in patients with average-risk (AR) medulloblastoma treated with craniospinal radiotherapy and four cycles of cisplatin-based, dose-intense chemotherapy and stem-cell rescue.
  
  
  METHODS
  The primary objective was to determine whether, in patients with AR medulloblastoma (n = 62), amifostine would decrease the need for hearing aids (defined as >or= grade 3 ototoxicity in one ear) compared with a control group (n = 35), 1 year from initiating treatment. Ninety-seven patients received craniospinal irradiation (23.4 Gy) followed by 55.8 Gy to the primary tumor bed using three-dimensional conformal technique, and four cycles of high-dose cyclophosphamide (4,000 mg/m(2)/cycle), cisplatin (75 mg/m(2)/cycle), and vincristine (two 1.5 mg/m(2) doses/cycle) and stem-cell rescue. When used, amifostine (600 mg/m(2)/dose) was administered as a bolus immediately before and 3 hours into the cisplatin infusion.
  
  
  RESULTS
  The median age of the 97 patients was 8.7 years (range, 3.2 to 20.2 years). The study and control groups were similar in age and sex distribution. Amifostine was well-tolerated. One year after treatment initiation, 13 patients (37.1%) in the control group versus nine (14.5%; one-sided chi(2) test P = .005) of the amifostine-treated patients had at least grade 3 ototoxicity, requiring hearing aid in at least one ear.
  
  
  CONCLUSIONS
  Amifostine administered before and during the cisplatin infusion can significantly reduce the risk of severe ototoxicity in patients with AR medulloblastoma receiving dose-intense chemotherapy.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA. maryam.fouladi@stjude.org
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: David
authors.initials: D
authors.lastname: Ashley
authors.forename: Stewart
authors.initials: S
authors.lastname: Kellie
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: Tim
authors.initials: T
authors.lastname: Hassall
authors.forename: Lindsey
authors.initials: L
authors.lastname: Gronewold
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Dana
authors.initials: D
authors.lastname: Wallace
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Brannon
authors.initials: B
authors.lastname: Morris
authors.forename: Matthew
authors.initials: M
authors.lastname: Krasin
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006310:Hearing Aids; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control* / Q000534:rehabilitation; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D011446:Prospective Studies; D018570:Risk Assessment; D033581:Stem Cell Transplantation; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide; D004999:Amifostine; D002945:Cisplatin