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

作者：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^*

来源：British Journal of Cancer, 2011, 104(4): 593-598.

DOI：10.1038/bjc.2011.6

• cisplatin
• DDS
• EPR effect
• NC-6004
• phase I study
• polymer micelle

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 mgm(-2) and was increased up to 120 mgm(-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 mgm(-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 mgm(-2), which led to the conclusion that the maximum tolerated dose was 120 mgm(-2), and the recommended dose was 90 mgm(-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 mgm(-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. British Journal of Cancer (2011) 104, 593-598. doi:10.1038/bjc.2011.6 www.bjcancer.

• 出版日期2011-2-15