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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

From the Departments of Oncology, Biostatistics, Pharmaceutical Sciences, Radiological Sciences, St Jude Children's Research Hospital, Memphis, TN; Baylor College of Medicine, Houston, TX, Royal Children's Hospital, Melbourne, Australia; Children's Hospital at Westmead, Sydney, Australia; Royal Children's Hospital, Brisbane, Australia; and The Preston Robert Tisch Brain Tumor Center and Departments of Pediatrics and Surgery, Duke University Medical Center, Durham, NC

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{at}stjude.org

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.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on www.JCO.org.

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Related Correspondence

• Prevention of Hearing Loss in Children Receiving Cisplatin Chemotherapy
  David R. Freyer, Lillian Sung, and Gregory H. Reaman
  JCO 2009 27: 317-318 [Full Text]

This article has been cited by other articles:

				D. R. Freyer, L. Sung, and G. H. Reaman Prevention of Hearing Loss in Children Receiving Cisplatin Chemotherapy J. Clin. Oncol., January 10, 2009; 27(2): 317 - 318. [Full Text] [PDF]

				M. Fouladi and A. Gajjar In Reply J. Clin. Oncol., January 10, 2009; 27(2): 318 - 319. [Full Text] [PDF]