A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours

Plummer, R.; Wilson, R.H.; Calvert, H.; Boddy, A.V.; Griffin, M.; Sludden, J.; Tilby, M.J.; Eatock, M.; Pearson, D.G.; Ottley, C.J.; Matsumura, Y.; Kataoka, K.; Nishiya, T.

Abstract

Background: On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study. Methods: A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10mgm−2 and was increased up to 120mgm−2 according to the accelerated titration method and modified Fibonacci method. Results: One dose-limiting toxicity (DLT) occurred in a patient who was given 90mgm−2 of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120mgm−2, which led to the conclusion that the maximum tolerated dose was 120mgm−2, and the recommended dose was 90mgm−2, although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration–time curve of ultrafilterable platinum at 120mgm−2 NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin. Conclusion: The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.

Citation

Plummer, R., Wilson, R., Calvert, H., Boddy, A., Griffin, M., Sludden, J., …Nishiya, T. (2011). A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours. British Journal of Cancer, 104(4), 593-598. https://doi.org/10.1038/bjc.2011.6

• Journal Article Type: Article
• Publication Date: Feb 1, 2011
• Deposit Date: Jan 18, 2012
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Springer Nature
• Peer Reviewed: Peer Reviewed
• Volume: 104
• Issue: 4
• Pages: 593-598
• DOI: https://doi.org/10.1038/bjc.2011.6
• Keywords: Cisplatin, DDS, EPR effect, NC-6004, Phase I study, Polymer micelle.
• Public URL: https://durham-repository.worktribe.com/output/1522175