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

Maryam Fouladi, Murali Chintagumpala, David Ashley, Stewart Kellie, Sridharan Gururangan, Tim Hassall, Lindsey Gronewold, Clinton F. Stewart, Dana Wallace, Alberto Broniscer, Gregory A. Hale, Kimberly A. Kasow, Thomas E. Merchant, Brannon Morris, Matthew Krasin, Larry E. Kun, James M. Boyett, Amar Gajjar

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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/m 2/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 χ2 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.

Original languageEnglish (US)
Pages (from-to)3749-3755
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number22
DOIs
StatePublished - Sep 22 2008

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Amifostine
Medulloblastoma
Cisplatin
Hearing Aids
Control Groups
Ear
Stem Cells
Craniospinal Irradiation
Drug Therapy
Sex Distribution
Age Distribution
Vincristine
Cyclophosphamide
Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fouladi, M., Chintagumpala, M., Ashley, D., Kellie, S., Gururangan, S., Hassall, T., ... Gajjar, A. (2008). Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma. Journal of Clinical Oncology, 26(22), 3749-3755. https://doi.org/10.1200/JCO.2007.14.3974

Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma. / Fouladi, Maryam; Chintagumpala, Murali; Ashley, David; Kellie, Stewart; Gururangan, Sridharan; Hassall, Tim; Gronewold, Lindsey; Stewart, Clinton F.; Wallace, Dana; Broniscer, Alberto; Hale, Gregory A.; Kasow, Kimberly A.; Merchant, Thomas E.; Morris, Brannon; Krasin, Matthew; Kun, Larry E.; Boyett, James M.; Gajjar, Amar.

In: Journal of Clinical Oncology, Vol. 26, No. 22, 22.09.2008, p. 3749-3755.

Research output: Contribution to journalArticle

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 2008, 'Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma', Journal of Clinical Oncology, vol. 26, no. 22, pp. 3749-3755. https://doi.org/10.1200/JCO.2007.14.3974
Fouladi, Maryam ; Chintagumpala, Murali ; Ashley, David ; Kellie, Stewart ; Gururangan, Sridharan ; Hassall, Tim ; Gronewold, Lindsey ; Stewart, Clinton F. ; Wallace, Dana ; Broniscer, Alberto ; Hale, Gregory A. ; Kasow, Kimberly A. ; Merchant, Thomas E. ; Morris, Brannon ; Krasin, Matthew ; Kun, Larry E. ; Boyett, James M. ; Gajjar, Amar. / Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 22. pp. 3749-3755.
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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/m 2/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 χ2 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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AU - Chintagumpala, Murali

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AU - Kellie, Stewart

AU - Gururangan, Sridharan

AU - Hassall, Tim

AU - Gronewold, Lindsey

AU - Stewart, Clinton F.

AU - Wallace, Dana

AU - Broniscer, Alberto

AU - Hale, Gregory A.

AU - Kasow, Kimberly A.

AU - Merchant, Thomas E.

AU - Morris, Brannon

AU - Krasin, Matthew

AU - Kun, Larry E.

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N2 - 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/m 2/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 χ2 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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