Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles

Wilson, Richard H.; Plummer, Ronda; Adam, Jean-François; Eatock, Martin; Boddy, Alan V.; Griffin, Melanie; Miller, Ryan; Matsumura, Yasuhiro; Shimizu, Takashi; Calvert, Hilary

doi:10.1200/jco.2008.26.15_suppl.2573

Cited by 29 publications

(13 citation statements)

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“…A phase I clinical trial of NC-6004 has recently been completed in the UK. (24) The starting dose of NC-6004 was 10 mg/m 2 . NC-6004 was administered once every 3 weeks with only 1000 mL water loading at the day of administration.…”

Section: Nc-6004: Cisplatin-incorporating Micellar Nanoparticlementioning

confidence: 99%

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

2009

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The size of anticancer agent-incorporating micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non-specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water-insoluble drug can be incorporated into polymer micelles. Presently, several anticancer agent-incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid-incorporating micelle carrier systems are also being developed. (Cancer Sci 2009; 100: 572-579) N anotechnology is one of the fast-moving technologies and is presently contributing significantly to the progress of medical science. Drugs categorized under the drug delivery system (DDS) are made primarily by utilizing nanotechnology. In the field of oncology, DDS drugs have been produced and evaluated in preclinical or clinical trials, with some already approved for clinical use (Table 1). More specifically, DDS can be used for active or passive targeting of tumor tissues. Passive targeting refers to the development of monoclonal antibodies directed against tumor-related molecules, allowing targeting of a tumor from the specific binding of antibodies with respective antigens. However, the application of DDS using monoclonal antibodies is restricted to tumors expressing high levels of related antigens.Passive targeting can be achieved by utilizing the enhanced permeability and retention (EPR) effect.(1,2) This effect is based on the pathophysiological characteristics of solid tumor tissues, namely, hypervascularity, incomplete vascular architecture, secretion of vascular permeability factors stimulating extravasation within cancer tissue, and absence of effective lymphatic drainage from tumors that impedes the efficient clearance of macromolecules accumulated in solid tumor tissues (Fig. 1A,B).Several techniques have been developed to maximally utilize the EPR effect such as modification of drug structures and development of drug carriers. Polymeric micelle-based anticancer drugs were originally developed by Kataoka et al. in the late 1980s or early 1990s. (3-5) Polymeric micelles were expected to increase the accumulation of drugs in tumor tissues by utilizing the EPR effect as well as to incorporate various kinds of drugs into their inner core with relatively high stability by chemical conjugation or physical entrapment. Also, the size of micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the r...

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Section: Nc-6004: Cisplatin-incorporating Micellar Nanoparticlementioning

confidence: 99%

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

2009

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“…Moreover, polymeric micelles can be designed to be responsive to environmental changes and capable of target recognition. Our micelle formulations incorporating Adriamycin, paclitaxel, SN-38, cisplatin, and DACHPt (activated oxaliplatin; NK911, NK105, NK012, NC6004, and NC4016, respectively) are being examined in clinical studies, and four of these formulations have advanced to phase II studies (18)(19)(20)(21). These clinical studies have revealed that polymeric micelles showed reduced side effects and high effectiveness against various intractable tumors, including triple-negative breast cancers that do not express the genes for estrogen receptor, progesterone receptor, and Her2/neu (22).…”

Section: Introductionmentioning

confidence: 99%

Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

et al. 2010

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Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)-based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r 1 of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the microsynchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential. Cancer Res; 70(18); 7031-41. ©2010 AACR.

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“…In a small phase I study, it was shown that NC-6004 was well-tolerated by patients suffering from colorectal carcinoma, upper gastrointestinal tumors, non-small-cell lung carcinoma (NSCLC), melanoma and other tumor types. 118,119 The pharmacokinetic analysis aer the administration of NC-6004 displayed prolonged circulation of in the blood, delayed and sustained release of potentially active Pt species. A lower C max for ultra-lterable Pt compared with that of non-protein-bound cisplatin, might be responsible for reduction of cisplatin related toxicity.…”

Section: Polymeric Micelles In Clinical Trialsmentioning

confidence: 99%

Clinical developments of antitumor polymer therapeutics

2019

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Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles

Cited by 29 publications

References 0 publications

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles

Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Clinical developments of antitumor polymer therapeutics

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