Hirai, Ikuko

写真a

Affiliation

School of Medicine, Department of Dermatology （Shinanomachi）

Position

Instructor
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Career 【 Display / hide 】

  • 2008.04
    -
    Present

    Department of Dermatology, Keio University School of Medicine

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Academic Background 【 Display / hide 】

  • 　

    Nippon Medical School

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Research Areas 【 Display / hide 】

  • Dermatology

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Research Keywords 【 Display / hide 】

  • skin cancer

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Research Themes 【 Display / hide 】

  • adoptive cell therapy using cultured tumor infiltrating lymphocytes with lympho-depleting non-myeloablative preconditioning for patients with metastatic melanoma, 

    2014.04
    -
    2017.03

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Papers 【 Display / hide 】

  • Serum cytokeratin 19 fragment 21-1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget disease

    Nakamura Y., Tanese K., Hirai I., Amagai M., Kawakami Y., Funakoshi T.

    British Journal of Dermatology （British Journal of Dermatology)  181 （ 3 ） 535 - 543 2019.09

    ISSN  00070963

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    © 2019 British Association of Dermatologists Background: Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma affecting the genitals and axillary regions. As metastasis of these tumours is itself rare, solid disease management strategies have not been established. Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) levels have been identified as candidate biomarkers for tumour progression in EMPD. Objectives: To determine the accuracy of and the correlation between these markers in patients with EMPD. Methods: Serum CEA and CYFRA 21-1 levels were examined in 30 patients with EMPD treated at Keio University Hospital, and compared against clinical information. Both assays were performed at the time of diagnosis, during the postoperative observation period, and following systemic treatment in those with confirmed metastasis. Serum levels were then correlated with tumour progression status and treatment responses. Results: Normal levels for both assays were observed in all 11 patients with primary localized disease (100%). In patients with metastatic disease the CEA positivity rate was 79% (15 of 19 patients), with a rate of 63% (12 of 19 patients) for CYFRA 21-1. Changes in CEA and CYFRA 21-1 levels were statistically independent; however, using a combined view, elevated levels of either marker improved the positivity rate to 95% (18 of 19 patients). Use of both markers also correlated well with treatment responses. Conclusions: The combination of CEA and CYFRA 21-1 is useful for predicting metastasis and treatment response in patients with EMPD, especially in those who only have elevation of a single marker. What's already known about this topic?. Serum levels of carcinoembryonic antigen (CEA) and cytokine 19 fragment 21-1 (CYFRA 21-1) have been shown to be elevated in patients with extramammary Paget disease (EMPD). Elevation of serum CEA levels is associated with tumour progression of EMPD. A single small study reported that serum CYFRA 21-1 levels are elevated in patients with EMPD with lymph node metastasis. What does this study add?. Serum CEA and CYFRA 21-1 were present in 79% and 63% of 19 cases of metastatic EMPD, respectively. Elevations of CEA and CYFRA 21-1 were statistically independent. CEA and CYFRA 21-1 combination assays were positive in 95% of cases of metastatic EMPD. What is the translational message?. Combination assays with CEA and CYFRA 21-1 are useful for monitoring treatment response in patients with metastatic EMPD, particularly in those with elevation of either marker.

  • Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease

    Hirai I., Tanese K., Nakamura Y., Ishii M., Kawakami Y., Funakoshi T.

    Oncologist （Oncologist)  24 （ 6 ） e394 - e396 2019.06

    ISSN  10837159

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    © AlphaMed Press 2019 Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that clinicopathologically resembles breast cancer. The prognosis of metastatic EMPD is poor. Although several chemotherapies have been tried, the effects are temporary; better drugs and combinations are required. In the present study, we retrospectively analyze the efficacy and safety of combination of cisplatin, epirubicin, and paclitaxel in five metastatic EMPD cases. The efficacy was better than that for previously reported regimens: 80% partial responses, including two patients who were refractory to taxane- and/or platinum-based regimens. In terms of safety, four patients who were able to continue treatment exhibited acceptable tolerability. This is the first regimen to combine taxane and anthracycline. When treating breast cancer, anthracycline is regarded as the key cytotoxic agent, and anthracycline in combination with taxane constitutes a key chemotherapeutic regimen. Given our results, we speculate both drugs are critical chemotherapeutic agents for the treatment of metastatic EMPD.

  • Updates on the systemic treatment of advanced non-melanoma skin cancer

    Tanese K., Nakamura Y., Hirai I., Funakoshi T.

    Frontiers in Medicine （Frontiers in Medicine)  6 2019

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    © 2019 Tanese, Nakamura, Hirai and Funakoshi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Non-melanoma skin cancers (NMSCs), which represent a diverse group of cutaneous malignancies, are the most common forms of human neoplasia. The incidence of these diseases is increasing due to a number of factors, including that of increasing human lifespans. The majority of NMSCs are basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC), with the remainder being various rare skin cancers, including extramammary Paget's disease (EMPD), Merkel cell carcinoma (MCC), and several skin adnexal carcinomas. Of these, MCC usually shows aggressive behavior with a high mortality rate. On the other hand, BCC, cSCC, EMPD, and skin adnexal tumors usually show an indolent clinical course and metastasize only rarely. Nevertheless, the metastatic forms of these tumors commonly lead to poor patient outcome. A definitive management strategy for the treatment of advanced NMSC has not been established, mainly due to their rarity and lack of reliable information based on well-controlled randomized trials. Chemotherapeutic regimens for treatment of these diseases have been mainly based on the observations of isolated, small case series or clinical trials with a limited numbers of patients. However, accumulating evidence regarding their pathobiological backgrounds as well as recent advances in molecular biotechnology have facilitated the development of novel drugs for treatment of these diseases. Over the past decade, the U.S. Food and Drug Administration has approved several molecular targeting therapies, including Hedgehog inhibitors for BCC, monoclonal antibodies targeting anti-programmed death ligand-1 and anti- programmed cell death 1 (PD-1) for MCC, and anti-PD-1 for cSCC. Here, we review their clinical utility and discuss updated systemic treatment strategies for advanced NMSC.

  • Assessment of the methods used to detect HER2-positive advanced extramammary Paget’s disease

    Hirai Ikuko

    Medical Oncology 35   92 2018

  • Modified weekly regimen of cisplatin, epirubicin and paclitaxel induced a durable response in two cases of metastatic extramammary Paget's disease

    Hirai, I. and Funakoshi, T.

    J Dermatol 44 （ 10 ） 1148 - 1151 2017.10

    ISSN  1346-8138

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    Metastatic extramammary Paget's disease (EMPD) is a rare cancer with no standardized treatment. We report two cases of metastatic EMPD treated with a modified weekly PET (cisplatin, epirubicin and paclitaxel) regimen given biweekly (i.e. 2 weeks on/2 weeks off) that had durable responses. Case 1 was a 74-year-old man with EMPD metastatic to lymph nodes, lung, and bone who presented with a hemorrhagic tumor on the scrotum. We tried the PET regimen weekly, but adjusted the interval to biweekly after two doses because of hematological side-effects. After five doses, he showed a partial response (PR) on imaging, including the bone lesions. The lesions have remained the same size for 1 year. Case 2 was a 65-year-old man with EMPD metastatic to a right inguinal lymph node who presented with an erosive tumor on the scrotum. He was started on weekly docetaxel. However, the lymph node grew and iliac lymph node metastasis developed. Therefore, we tried the PET regimen with a 2 weeks on/2 weeks off schedule. After five doses, he showed a PR. In both cases, all adverse effects were manageable and this modified regimen could be administrated on an outpatient basis. With no current validated chemotherapy regimen, clinicians may consider a modified weekly PET regimen in future treatment of metastatic EMPD.

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Analysis of HER2 expression in metastatic extramammary Paget’s disease.

    Hirai Ikuko

    World Congress on Cancers of the Skin 2018, 2018.08, Poster (general)

  • 進行期悪性黒色腫に対する骨髄非破壊的前処置および低用量IL-2併用の抗腫瘍自己リンパ球輸注療法feasibility試験

    Hirai Ikuko

    第22回 日本がん免疫学会総会　 (岡山市) , 2018.08, Oral Presentation(general)

  • 進行期悪性黒色腫に対する骨髄非破壊的前処置および低用量IL-2併用の抗腫瘍自己リンパ球輸注療法

    Hirai Ikuko

    第34回日本皮膚悪性腫瘍学会学術大会　 (浜松市) , 2018.07, Oral Presentation(general)

  • Weekly cisplatin, epirubicin, and paclitaxel induced a durable response in two cases of metastatic extramammary Paget’s disease.

    Hirai Ikuko

    2016.08, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 進行期乳房外パジェット病における治療効果予測のバイオマーカーの探索

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 平井 郁子, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • ［革新的がん医療実用化研究事業］ 進行期悪性黒色腫(末端黒子型)に対する非骨髄破壊性前処置併用での腫瘍浸潤Tリンパ球輸注療法の安全性試験

    2015
    -
    2017

    AMED（国立研究開発法人日本医療研究開発機構）, 河上　裕

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Memberships in Academic Societies 【 Display / hide 】

  • Japanese Dermatological Association

    　
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