Delayed sodium thiosulfate as an otoprotectant against carboplatin-inducedhearing loss in patients with malignant brain tumors

Carboplatin is effective in the treatment of malignant brain tumors. Howeve r, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic, The purpose of this study was to d etermine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity, Pat ients underwent monthly treatment with intra-arterial carboplatin (200 mg/m (2)/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 ye ar. audiological assessment was conducted at baseline and within 24 h befor e each monthly treatment. STS was administered i.v. as one (20 g/m(2)) or t wo (20 g/m(2) and 16 g/m(2)) 15-min doses, depending on baseline hearing st atus. The initial group received the first STS dose 2 h (or 2 and 6 h) afte r carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historica l comparison group (HCG) treated with carboplatin without STS, Spearman cor relation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased dela y in STS (P = 0.0006), On the basis of the analysis of hearing levels, ther e 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 oto toxicity indicated a significant difference between STS4 and HCG (P = 0.001 8), Delayed STS was effective in protecting against carboplatin-induced hea ring loss. STS delayed to 4 h after carboplatin significantly decreased tim e to development of ototoxicity and rate of ototoxicity when compared with HCG.