Carboplatin is effective in the treatment of malignant
brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB),
carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of
sodium thiosulfate (STS), given after BBB closure, provided protection against
carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial
carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after
carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after
carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with
carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of
ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to
ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against
carboplatin-induced
hearing loss. STS delayed to 4 h after
carboplatin significantly decreased time to development of
ototoxicity and rate of
ototoxicity when compared with HCG.