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Drug Delivery System Vol. 32(2017) No. 2
Clinical application of DDS in cancer chemotherapy

[Feature articles]“Clinical application of DDS in cancer chemotherapy” Editor:Tetsuya Hamaguchi

[FOREWORD] Clinical application of DDS in cancer chemotherapy

Tetsuya Hamaguchi

Released: June 25, 2017

p.93

Full Text PDF[177K]

[OPINION] The 30th anniversary of the first appearance of the EPR effect

Yasuhiro Matsumura

Released: June 25, 2017

p.94

Full Text PDF[185K]

[MOURNING] Memory of Prof. Kenji Kono

Yuichi Ohya

Released: June 25, 2017

p.95-97

Full Text PDF[387K]

CPX-351, a liposomal formulation of cytarabine and daunorubicin against AML

Yukio Kobayashi

Released: June 25, 2017

p.100-108

The standard therapy of acute myeloid leukemia is a combination of cytarabine and daunorubicin. The standard doses of these drugs are 100 - 200mg/sqm for consecutive 7 days, and 90 mg/sqm for 3 injections, respectively, against younger patients, and 100 - 200mg/sqm for consecutive 7 days, and 45 mg/sqm for 3 injections, against elderly patients. There are debates on the doses of these agents. As cytarabine has a short half time of serum level when injected subcutaneously or intravenously, continuous intravenous injection was preferentially used. Intra-cellular ara-CTP, which is an active derivative of cytarabine, which exerts as killing activity in leukemic cells, is saturated when intravenous shot of as much as 3000 mg/sqm of cytarabine, high dose ara-CTP is another standard dose utilized for consolidation or maintenance therapy. The most effective dose of daunorubicin has been determined by clinical trials comparing the dose. In younger patients, 90 mg/sqm x 3 days had longer EFS than 45 mg/sqm in patients younger than 60 years, while there was no difference among patients older than 60 years old. CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. The drug is infused over 90 minutes on days 1, 3, and 5. Phase I and II study has shown the efficacy in patients with secondary AML. Recently, a phase III data were presented in ASCO meeting 2016. The study compared CPX-351 with a combination of cytarabine and daunorubicin. The doses of these two agents were, 100 mg/sqm for consecutive 7 days, and 60 mg/sqm for three days, respectively. The phase III result showed that OS, an endpoint of this study as well as EFS, and CR rate was significantly higher in the CPX-351. Although, there is a dispute on the selectin of the control arm in the dose of cytarabine and daunorubicin, this is a remarkable result that showed better OS than standard therapy for the first time in this decade.

Nanoliposomal irinotecan for patients with metastatic pancreatic cancer

Yoshiyuki Yamamoto

Released: June 25, 2017

p.109-118

Some anticancer agents-incorporating liposomes have been developed and exhibited the clinical benefits. Recently, a novel nanoliposomal formulation of irinotecan (Onyvide^®) has been approved in combination with 5―FU and leucovorin for the treatment of patients with metastatic pancreatic cancer. In this review, we introduce the characteristics and clinical trials of the nanoliposomal irinotecan.

Clinical development of T-DM1

Akitaka Makiyama

Released: June 25, 2017

p.119-125

T-DM1 is an antibody-drug conjugate in which an anti-HER2 monoclonal antibody, trastuzumab, is linked to a tubulin polymerization inhibitor, DM1. T-DM1 is taken up by HER2-positive cells (internalization) and then cytotoxic DM-1 is released, inducing cell death. National health insurance was extended to cover the use of T-DM1 to treat HER2-positive breast cancer that had previously been treated with trastuzumab, but its subsequent clinical development was not an easy process but instead a series of failures. This is because T-DM1 is only effective against cells to which trastuzumab is bound, representing a glaring flaw in this groundbreaking drug delivery system. In other words, the development of T-DM1 failed while HER2 loss was not taken into account. HER2 loss is a phenomenon whereby modification, i.e. anti-HER2 therapy, causes a change in HER2 status in a heterogeneous tumor consisting of some cells that are HER2-positive and some that are HER2-negative. New antibody-drug conjugates should be developed in the future with this point in mind.

Brentuximab vedotin. an antibody-drug conjugate targeting CD30

Tomoko Yanai

Released: June 25, 2017

p.126-133

Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, is indicated for the treatment of CD30-positive relapsed/refractory Hodgkin’s lymphoma and anaplastic large cell lymphoma. When BV is internalized by CD30-positive cells, MMAE binds to microtubules to induce apoptosis. Clinically significant adverse reactions to BV include peripheral nerve disorder, infection, bone marrow suppression, and infusion reaction. The efficacy and safety of BV used in combination with other antitumor drugs have not been established. The results of multinational Phase III clinical studies of BV with chemotherapy in untreated HL and untreated CD30-positive mature T-cell lymphoma are anticipated.

The history of Granulocyte-colony stimulating factor

Momoko Takahashi, Chihiro Kondoh, Toshimi Takano

Released: June 25, 2017

p.134-142

Granulocyte-colony stimulating factor is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Pegylated G-CSF(pegfilgrastim), in which the addition of polyethylene glycol increases the half-life of the agent, decreases the incidence of febrile neutropenia during chemotherapy. The use of G-CSF support is also important to increase dose intensity or dose density of chemotherapy. Pegylated materials are expected to play an important role in cancer treatment.

Clinical development of the novel micellar compound in oncology area

Atsushi Osada

Released: June 25, 2017

p.143-148

Drug Delivery System (DDS) has been utilized in drug development since before and the various DDS compounds were developed in a variety of therapeutic areas. So far three Antibody-Drug Conjugate (ADC) compounds were launched in oncology field and a lot of new ADC compounds are under developing. Also novel DDS compounds applied by the state-of-the-art technology are being investigated globally, therefore the development competition would be continuing. NanoCarrier Co., Ltd. researches and develops new anticancer drugs utilizing the micellar nanoparticles technology. Three compounds are in clinical phase. In this article the characteristics of clinical development of the novel micellar compounds would be summarized based on my experiences.

[Serial] Reviews on useful reagents for DDS research and development

Solvent selection for research in laboratory

Masayuki Yokoyama, Kouichi Shiraishi

Released: June 25, 2017

p.150-152

Full Text PDF[302K]

“Young square”(mini review)

Thermoresponsive ureido polymers exhibiting UCST-type solution behavior under physiological conditions.

Naohiko Shimada

Released: June 25, 2017

p.154-155

Full Text PDF[517K]

Biomimetic strategy for development of pleiotropic DDS carriers

Masaharu Somiya

Released: June 25, 2017

p.156-157

Full Text PDF[351K]

1 - 12 / 12 Articles.

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Volume And Issue List
Drug Delivery System

Drug Delivery System Vol. 32(2017) No. 2
Clinical application of DDS in cancer chemotherapy

[Feature articles]“Clinical application of DDS in cancer chemotherapy” Editor:Tetsuya Hamaguchi

[FOREWORD] Clinical application of DDS in cancer chemotherapy

[OPINION] The 30th anniversary of the first appearance of the EPR effect

[MOURNING] Memory of Prof. Kenji Kono

CPX-351, a liposomal formulation of cytarabine and daunorubicin against AML

Nanoliposomal irinotecan for patients with metastatic pancreatic cancer

Clinical development of T-DM1

Brentuximab vedotin. an antibody-drug conjugate targeting CD30

The history of Granulocyte-colony stimulating factor

Clinical development of the novel micellar compound in oncology area

[Serial] Reviews on useful reagents for DDS research and development

Solvent selection for research in laboratory

“Young square”(mini review)

Thermoresponsive ureido polymers exhibiting UCST-type solution behavior under physiological conditions.

Biomimetic strategy for development of pleiotropic DDS carriers

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Announcement From J-STAGE

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Volume And Issue List Drug Delivery System

Drug Delivery System Vol. 32(2017) No. 2 Clinical application of DDS in cancer chemotherapy

[Feature articles]“Clinical application of DDS in cancer chemotherapy” Editor:Tetsuya Hamaguchi

[Serial] Reviews on useful reagents for DDS research and development

“Young square”(mini review)

System Maintenance

Announcement From J-STAGE

Journal Tools

Share this Title

Volume And Issue List
Drug Delivery System

Drug Delivery System Vol. 32(2017) No. 2
Clinical application of DDS in cancer chemotherapy