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Lookup NU author(s): Professor Gareth Veal, Melanie Griffin, Annie Parry, Dr Juliet Hale, Professor Andrew Pearson, Professor Alan Boddy
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Pre-clinical studies indicate that cisplatin encapsulated in STEALTH® liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m-2 by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin. © 2001 Cancer Research Campaign.
Author(s): Veal, G. J., Griffin, M., Price, E., Parry, A. P., Dick, G., Little, M., Yule, S., Morland, B., Estlin, E., Hale, J. P., Pearson, A. D. J., Welbank, H., Boddy, A. V.
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2001
Volume: 84
Issue: 8
Pages: 1029-1035
Print publication date: 20/04/2001
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
URL: http://dx.doi.org/10.1054/bjoc.2001.1723
DOI: 10.1054/bjoc.2001.1723
PubMed id: 11308249
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