A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors

@article{Mukai2016AFP,
  title={A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors},
  author={Hirofumi Mukai and Takahiro Kogawa and Nobuaki Matsubara and Yoichi Naito and Masaoki Sasaki and Ako Hosono},
  journal={Investigational New Drugs},
  year={2016},
  volume={35},
  pages={307-314}
}
SummaryBackground K-912 also known as NC-6300 is a novel epirubicin pro-drug conjugate developed using micellar nanoparticle technology. We conducted a first-in-human, Phase 1, open-label, non-randomized dose escalation study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of K-912 administered as monotherapy in patients with advanced or recurrent solid tumors. Methods Patients aged 41 to 72 years with histologically or cytologically confirmed advanced or recurrent… 
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47 Citations
Highly Influential Citations
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Background Citations
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Methods Citations
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47 Citations

A Phase 1b Dose Escalation Trial of NC-6300 (Nanoparticle Epirubicin) in Patients with Advanced Solid Tumors or Advanced, Metastatic, or Unresectable Soft-tissue Sarcoma
TLDR
NC-6300 was well tolerated with a manageable side effect profile, despite the MTD and RP2D being higher than conventional epirubicin doses, and warrants further investigation in patients with advanced solid tumors, including sarcoma.
Anthracyclines
Anthracyclines are a clinically important class of antineoplastic agents used to treat a wide variety of solid and blood cancers. The first described anthracycline, daunorubicin, was first isolated…
Epirubicin‐loaded polymeric micelles effectively treat axillary lymph nodes metastasis of breast cancer through selective accumulation and pH‐triggered drug release
Reinforcement of antitumor effect of micelles containing anticancer drugs by binding of an anti-tissue factor antibody without direct cytocidal effects.
Efficacy of pH-Sensitive Nanomedicines in Tumors with Different c-MYC Expression Depends on the Intratumoral Activation Profile.
TLDR
Tumor-targeted nanomedicines capable of treating both tumors with high and low c-Myc levels by adjusting their ability to spatiotemporally control drug action are developed and indicate the potential of engineered nanomediines for c- myelocytomatosis inhibition and spur the idea of precision pH-sensitive nanomedicsine based on cancer biomarker levels.
Polymer-drug conjugates: Design principles, emerging synthetic strategies and clinical overview.
Recent advances in developing polymeric micelles for treating cancer: breakthroughs and bottlenecks in their clinical translation
Effective treatment of drug resistant recurrent breast tumors harboring cancer stem‐like cells by staurosporine/epirubicin co‐loaded polymeric micelles
Effects of block copolymer micelles on the pharmacokinetics of encapsulated drugs
RNA‐Peptide nanoplexes drug DNA damage pathways in high‐grade serous ovarian tumors
TLDR
The development of a nanoscale peptide‐nucleic acid complex that facilitates tumor‐specific RNA interference therapy to chemosensitize advanced ovarian tumors to frontline platinum/taxane therapy and combined inhibition of MK2 could improve treatment outcomes in patients currently receiving frontline chemotherapy for advanced OC are reported.
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