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Clin Cancer Res. 2008 Jan 15;14(2):533-40. doi: 10.1158/1078-0432.CCR-06-2289.

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

Author information

1
Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Keck School of Medicine, University of Southern California and Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

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.

PMID:
18223229
DOI:
10.1158/1078-0432.CCR-06-2289
[Indexed for MEDLINE]
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