Amifostine protects against cisplatin-induced ototoxicity in children with
average-risk medulloblastoma 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. J
Clin Oncol. 2008 Aug 1;26(22):3749-55


Corresponding author: Maryam Fouladi, MD, Department of Oncology, St Jude
Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794;
e-mail: maryam.fouladi@...



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 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/m2/cycle), cisplatin (75 mg/m2/cycle), and
vincristine (two 1.5 mg/m2 doses/cycle) and stem-cell rescue. When used,
amifostine (600 mg/m2/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 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.
Supported in part by National Cancer Institute Grant No. P30 CA21765, the
Pediatric Brain Tumor Foundation, the Noyes Brain Tumor Foundation, Musicians
Against Childhood Cancer, the Ryan McGhee Foundation, and the American Lebanese
Syrian Associated Charities.

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