- Author
- 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
- Title
- Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma.
- Publication Date
- 8/1/2008
- Pages
- 3749-55
- Journal Name
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Abstract
- 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.
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