A Phase I Clinical Study of Cisplatin-Incorporated Polymeric Micelles (NC-6004) in Patients with Solid Tumors

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

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290 Citations (Scopus)

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 10?mg?m(-2) and was increased up to 120?mg?m(-2) according to the accelerated titration method and modified Fibonacci method. RESULTS: One dose-limiting toxicity (DLT) occurred in a patient who was given 90?mg?m(-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 120?mg?m(-2), which led to the conclusion that the maximum tolerated dose was 120?mg?m(-2), and the recommended dose was 90?mg?m(-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 120?mg?m(-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.
Original languageEnglish
Pages (from-to)593-598
Number of pages6
JournalBritish Journal of Cancer
Volume104 (4)
Issue number4
DOIs
Publication statusPublished - 15 Feb 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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