Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma.

Journal Article (Journal Article)

PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Fouladi, M; Chintagumpala, M; Ashley, D; Kellie, S; Gururangan, S; Hassall, T; Gronewold, L; Stewart, CF; Wallace, D; Broniscer, A; Hale, GA; Kasow, KA; Merchant, TE; Morris, B; Krasin, M; Kun, LE; Boyett, JM; Gajjar, A

Published Date

  • August 1, 2008

Published In

Volume / Issue

  • 26 / 22

Start / End Page

  • 3749 - 3755

PubMed ID

  • 18669462

Pubmed Central ID

  • PMC2504739

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2007.14.3974


  • eng

Conference Location

  • United States