Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma.
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.
Fouladi
Maryam
M
Department of Oncology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA. maryam.fouladi@stjude.org
Chintagumpala
Murali
M
Ashley
David
D
Kellie
Stewart
S
Gururangan
Sridharan
S
Hassall
Tim
T
Gronewold
Lindsey
L
Stewart
Clinton F
CF
Wallace
Dana
D
Broniscer
Alberto
A
Hale
Gregory A
GA
Kasow
Kimberly A
KA
Merchant
Thomas E
TE
Morris
Brannon
B
Krasin
Matthew
M
Kun
Larry E
LE
Boyett
James M
JM
Gajjar
Amar
A
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
D014750:Vincristine; D003520:Cyclophosphamide; D004999:Amifostine; D002945:Cisplatin