Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity

Theresa M. Harned, Ondrej Kalous, Alexander Neuwelt, Jason Loera, Lingyun Ji, Peter Iovine, Richard Sposto, Edward A. Neuwelt, C. Patrick Reynolds

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Abstract

Purpose: We determined if the potentially otoprotective agent sodium thiosulfate (STS) could be given 6 h after cisplatin without diminishing the antineuroblastoma activity of cisplatin in human neuroblastoma cell lines in vitro (including cisplatin-resistant cell lines) and in neuroblastoma xenografts in vivo. Experimental Design: We determined the antineuroblastoma activity of cisplatin with or without the addition of STS at 0 or 6 h after cisplatin in six neuroblastoma cell lines, both in standard cell culture conditions (20% O 2) and in physiologic hypoxia (2% O2). Drug cytotoxicity was measured using the DIMSCAN fluorescence/digital imaging microscopy assay. In vivo studies of cisplatin combined with STS used a human neuroblastoma subcutaneous xenograft model (SMS-SAN) in athymic nu/numice. Results: A significant protection against cisplatin cytotoxicity was seen when the neuroblastoma cells were exposed to cisplatin directly combined with STS. However, when cisplatin was given first and STS exposure occurred 6 h later, no effect on cisplatin cytotoxicity was observed. In a subcutaneous neuroblastoma xenograft model in nu/nu mice, mice receiving cisplatin alone or cisplatin + STS at 6 h had significantly better progression-free survival rates (P < 0.03) compared with controls or mice treated with cisplatin + STS concurrently. There was no statistically significant difference in outcomes between mice treated with cisplatin alone and the group treated with cisplatin followed by STS 6 h later (P = 0.9). Conclusion: These preclinicaldata suggest that theuse of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.

Original languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number2
DOIs
StatePublished - Jan 15 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Harned, T. M., Kalous, O., Neuwelt, A., Loera, J., Ji, L., Iovine, P., Sposto, R., Neuwelt, E. A., & Reynolds, C. P. (2008). Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity. Clinical Cancer Research, 14(2), 533-540. https://doi.org/10.1158/1078-0432.CCR-06-2289