• Cancer research · Feb 1996

    In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity.

    • E A Neuwelt, R E Brummett, L G Remsen, R A Kroll, M A Pagel, C I McCormick, S Guitjens, and L L Muldoon.
    • Department of Neurology, Oregon Health Sciences University, Portland 97201 USA.
    • Cancer Res. 1996 Feb 15; 56 (4): 706-9.

    AbstractWhen carboplatin (cis-diammine-1,1-cyclobutane-dicarboxylato-platinum) delivery to brain tumors is optimized with osmotic blood-brain barrier disruption (BBBD), high frequency hearing loss can result. Treatment with sodium thiosulfate (STS) blocked carboplatin cytotoxicity against the LX-1 human small cell lung carcinoma cell line in vitro. STS decreased carboplatin-induced ototoxicity in a guinea pig model, as determined by electrophysiological measurements and analysis of inner ear outer hair cell numbers. Protection was found when STS was administered up to 8 h subsequent to carboplatin but not 24 h after carboplatin. In a rat model of osmotic BBBD, STS was neurotoxic when given immediately after BBBD but not when given 60 min after BBBD, when the barrier is reestablished. Thus, delayed administration of STS may provide a mechanism to reduce the cochlear toxicity caused by BBBD-enhanced carboplatin delivery to the brain.

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