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 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 < 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.