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

Plummer, R. and Wilson, R. H. and Calvert, H. and Boddy, A. V. and Griffin, M. and Sludden, J. and Tilby, M. J. and Eatock, M. and Pearson, D. G. and Ottley, C. J. and Matsumura, Y. and Kataoka, K. and 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). pp. 593-598.


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.

Item Type:Article
Additional Information:Full-text available at:
Keywords:Cisplatin, DDS, EPR effect, NC-6004, Phase I study, Polymer micelle.
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Date accepted:No date available
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Date of first online publication:February 2011
Date first made open access:No date available

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