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

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 4 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 to a control group (n=35), one year from initiating treatment. (Figure 1) Ninety-seven patients received CSI (23.4 Gy) followed by 55.8 Gy to the primary tumor bed, using 3-D conformal technique and 4 cycles of high-dose cyclophosphamide (4000 mg/m(2) per cycle), cisplatin (75 mg/m(2) per cycle), and vincristine (two 1.5 mg/m(2) doses per cycle) and stem cell rescue. When used, amifostine (600 mg/m(2) per dose) was given as a bolus immediately prior to and 3 hours into the cisplatin infusion. RESULTS: The median age of the 97 patients was 8.7 years (range, 3.2–20.2 years). The study and control groups were similar in age and sex distribution. Amifostine was well-tolerated. One year after treatment initiation, 13 (37.1%) of the control-group versus 9 (14.5%; p=0.005 Chi-Square one-sided test) of the amifostine-treated patients had ≥ grade 3 ototoxicity, requiring hearing aid in at least one ear. CONCLUSION: Amifostine administered prior to and during the cisplatin infusion can significantly reduce the risk of severe ototoxicity in patients with AR medulloblastoma receiving dose-intense chemotherapy