Cisplatin is retained in the cochlea indefinitely following chemotherapy

Andrew M. Breglio, Aaron E. Rusheen, Eric D. Shide, Katharine A. Fernandez, Katie K. Spielbauer, Katherine M. McLachlin, Matthew D. Hall, Lauren Amable and Lisa L. Cunningham ()
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Andrew M. Breglio: National Institutes of Health
Aaron E. Rusheen: National Institutes of Health
Eric D. Shide: National Institutes of Health
Katharine A. Fernandez: National Institutes of Health
Katie K. Spielbauer: National Institutes of Health
Katherine M. McLachlin: Electro Scientific Industries, Inc.
Matthew D. Hall: National Institutes of Health
Lauren Amable: National Institutes of Health
Lisa L. Cunningham: National Institutes of Health

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Cisplatin chemotherapy causes permanent hearing loss in 40–80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetics in the cochleae of mice and humans. In most organs cisplatin is detected within one hour after injection, and is eliminated over the following days to weeks. In contrast, the cochlea retains cisplatin for months to years after treatment in both mice and humans. Using laser ablation coupled to ICP-MS, we map cisplatin distribution within the human cochlea. Cisplatin accumulation is consistently high in the stria vascularis, the region of the cochlea that maintains the ionic composition of endolymph. Our results demonstrate long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity.

Date: 2017
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DOI: 10.1038/s41467-017-01837-1

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