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

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% O(2)). 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/nu mice.

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 preclinical data suggest that the use of STS 6 h after cisplatin for otoprotection is unlikely to compromise the antineuroblastoma activity of cisplatin.

• Authors: Theresa M Harned, Ondrej Kalous, Alexander Neuwelt, Jason Loera, Lingyun Ji, Peter Iovine, Richard Sposto, Edward A Neuwelt, C Patrick Reynolds
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 2 Pg. 533-40 (Jan 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18223229 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Radiation-Sensitizing Agents
• Thiosulfates
• Carboplatin
• sodium thiosulfate
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use, toxicity)
• Carboplatin (therapeutic use, toxicity)
• Cell Hypoxia
• Cell Line, Tumor
• Cisplatin (pharmacokinetics, therapeutic use, toxicity)
• Humans
• Mice
• Mice, Nude
• Neuroblastoma (drug therapy, metabolism)
• Radiation-Sensitizing Agents (therapeutic use, toxicity)
• Thiosulfates (administration & dosage, pharmacokinetics, therapeutic use)
• Xenograft Model Antitumor Assays