Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer

Matsumura, Yasuhiro; Gotoh, Mitsukazu; Muro, Kei; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro; Okuwa, Mayumi; Matsumoto, Shin; Miyata, Yosihisa; Ohkura, H; Chin, K.; Baba, Shinichi; Yamao, Takekazu; Kannami, Ayako; Takamatsu, Yasuo; Ito, Kaori; Takahashi, Kazunori

doi:10.1093/annonc/mdh092

Cited by 221 publications

(84 citation statements)

References 10 publications

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“…With respect to immunoliposomes, although many preclinical studies can be found in the literature [24,215,275,276] and a few clinical trials are in progress [18,75,[277][278][279] an siRNA that targets PKN3 [18,286], or TKM-PLK1 that includes siRNA against PLK1 for the treatment of neuroendocrine tumors and adrenocortical carcinomas (phase I/II clinical trials) [283,287,288]. The phase I liposomic formulation SGT-53 includes plasmidic DNA that expresses the tumor suppressor gene p53 to treat solid tumors [280,289].…”

Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,399

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,399

754

View full text Add to dashboard Cite

show abstract

“…66,67) Incorporation of EGF into PEGylated nanoparticles was also demonstrated for targeting to the EGF-R. [68][69][70] other molecules overexpressed on tumors such as nucleosome, cd19, membrane type 1 matrix metalloproteinase (MT1-MMP), GAH, Gd2, and heparinbinding EGF-like growth factor were targeted by immunoliposomes. [71][72][73][74][75][76][77] Aptamers are single-stranded dNA or RNA, can specifically bind molecules, and are beginning to be used as targeting ligands for drug delivery systems. [78][79][80][81] Peptides containing specific motifs in sequence which recognize specific molecules have been identified using phage-displayed peptide libraries.…”

Section: -28)mentioning

confidence: 99%

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Hatakeyama

Akita

Harashima

2013

Biological & Pharmaceutical Bulletin

415

276

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Gene and nucleic acid therapy is expected to play a major role in the next generation of agents for cancer treatment. We have recently developed a multifunctional envelope-type nano device (MEND) for use as a novel nonviral gene delivery system. The modification of polyethyleneglycol (PEG), i.e., PEGylation, is a useful method for achieving a longer circulation time for the delivery of MEND to a tumor via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity of the delivery system. For successful nucleic acid delivery for cancer treatment, the crucial problem associated with the use of PEG, i.e., the "PEG dilemma" must be resolved. In this review, we describe the development and applications of MEND and discuss various strategies for overcoming the PEG dilemma based on the manipulation of both pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release. To increase cellular uptake, target ligands including proteins, peptides, antibodies and aptamers that recognize molecules specifically expressed on tumors are first introduced. Second, cleavable PEG systems are described. The cleavage of PEG from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. Then, endosomal fusogenic peptides are discussed. Finally, pH-sensitive liposomes using pH-sensitive lipids are described.

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“…For example, anti-EGFR immunoliposomes encapsulating DOX have been shown to target the epidermal growth factor receptor by coupling Fab′ fragments of the Cetuximab monoclonal antibody on the surface of the liposomes [96,97]. MCC-465 is a PEGylated immunoliposome containing DOX, modified with the F(ab')2 fragment of GAH human monoclonal antibody, for the treatment of gastric cancer [97,98]. The delivery of DOX to the brain via liposomes has been enhanced by conjugation with glutathione.…”

Section: Clinical Experience With Liposomes For Cancer Chemotherapymentioning

confidence: 99%

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

Porfire¹,

Achim²,

Tefas³

et al. 2017

Liposomes

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The liposomes present great potential for applications in targeted delivery of chemotherapeutics in the treatment of cancer. The use of liposomal drug carriers as vehicles for targeting of chemotherapeutic agents to tumor tissues is based on their advantages over other dosage forms, represented by their low systemic toxicity, their bioavailability, and their possibility to enhance the solubility of different chemotherapeutic agents, due to the ability to encapsulate both hydrophilic and lipophilic drugs. They enhance the therapeutic index of anticancer drugs by increasing the drug concentration in tumor cells through tumor targeting. The available approaches used for tumor targeting using liposomes are passive targeting, active targeting, and triggered drug release. The most advanced targeting strategies proposed for cancer treatment are the development of multifunctional liposomes, having combined targeting mechanism. In this chapter, the tumor-targeting mechanisms are described in detail as well as the possibilities to design the targeted liposomal nanocarrier in order to reach the desired target in the body and minimizing the off-target effects. Moreover, the current status of preclinical and clinical evaluation is highlighted.

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Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer

Abstract: MCC-465 was well tolerated. The recommended dose for a phase II study of MCC-465, for a 3-week schedule, is considered to be 32.5 mg/m2 in an equivalent amount of DXR.

Cited by 221 publications

References 10 publications

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

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