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A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours
- Source :
- British Journal of Cancer
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
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 Refereed/Peer-reviewed
- Subjects :
- Adult
Male
Cancer Research
medicine.medical_specialty
Maximum Tolerated Dose
Organoplatinum Compounds
Polymers
cisplatin
Antineoplastic Agents
polymer micelle
Models, Biological
NC-6004
Micelle
Drug Administration Schedule
DDS
Clinical study
Neoplasms
Phase (matter)
medicine
Humans
In patient
Solid tumor
Micelles
Aged
Aged, 80 and over
Cisplatin
Polymeric micelles
Dose-Response Relationship, Drug
Chemistry
polymeric micelle
Middle Aged
EPR effect
Surgery
phase I study
phase 1 study
Polyglutamic Acid
Oncology
Maximum tolerated dose
Injections, Intravenous
Clinical Study
Disease Progression
Cancer research
Female
medicine.drug
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....6dbcee433075247086018ecced5f56da