Ototoxic Effect of Cisplatin in Children with Brain Tumors

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Abstract
Thirty-four children, age 2–19 years, with brain tumors were treated with surgical resection, irradiation, and a cisplatin (CDDP) containing regimen. Audiologic assessments were conducted prior to each cycle of CDDP to monitor the ototoxic effects of CDDP. Twenty-eight patients with posterior fossa (PF) tumors received 5,040 to 5,650 cGy irradiation to the PF and 0–3,600 cGy to the remainder of the craniospinal (CS) axis. Six patients with supratentorial tumors received 5,140–5,580 cGy to the tumor site and 3,600–4,500 Gy to the remainder of the CS axis. Cycles of CDDP (68 mg/m2), lomustine (75 mg/m2), and vincristine (1.5 mg/m2 weekly for 3 weeks) were given every 6 weeks to 30 children immediately following irradiation, and to 4 at relapse. CDDP was infused over 8 h. Significant hearing loss, defined as a greater than 20-dB change from baseline in the hearing level (HL), occurred in the 250- to 2,000-Hz range in 4 of 29 patients receiving a cumulative dose (CD) of 410 mg/m2, and in 14 of 25 patients receiving a CD of 474 mg/m2. At 4,000 Hz, hearing sensitivity progressed from a HL of 20 ± 2 dB at a CD of 203 mg/m2 to 31 ± 6 dB (p 2 (p 2 (p 2 (p 20-dB changes in the 500- to 2,000-Hz range, meaningful data are not available at higher CDs for these frequencies. These data confirm the pattern of high-frequency hearing loss seen in children treated with CDDP, and suggest that the deleterious influence of cisplatin on hearing sensitivity at 4,000 and 8,000 Hz begins at a lower CD than in previously reported patients with non-central nervous system tumors who have not received cranial irradiation.

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