Ototoxic effect of cisplatin in children with brain tumors

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 (he 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 supratento-rial 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/m:). 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 fa. 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/nr. 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 <0.05) at a CD of 474 mg/m² (p <0.0001). At 8.000 Hz, hearing sensitivity progressed from a HL of 34 ± 4 dB at a CD of 203 mg/m² (p <0.05) to 54 ± 5 dB at a CD of 474 mg/m² (p <0.0001). Because the CDDP dosage was significantly reduced or eliminated in the children with >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.