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A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with...

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Autores principales: Yoshida, Soichiro, Takahara, Taro, Arita, Yuki, Ito, Masaya, Hayakawa, Sara, Oguchi, Tomohiko, Komai, Yoshinobu, Numao, Noboru, Yuasa, Takeshi, Inoue, Masaharu, Ushijima, Hiroki, Kudo, Shigehiro, Shimano, Yasumasa, Nakamura, Yuki, Uchida, Yusuke, Uehara, Sho, Tanaka, Hajime, Yaegashi, Hiroshi, Izumi, Kouji, Yokoyama, Minato, Matsuoka, Yoh, Yoshioka, Yasuo, Konishi, Koji, Nakanishi, Katsuyuki, Nagahara, Akira, Hirakawa, Akihiro, Koike, Ryuji, Koga, Fumitaka, Nishimura, Kazuo, Mizokami, Atsushi, Yonese, Junji, Kageyama, Yukio, Yoshimura, Ryoichi, Fujii, Yasuhisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987040/
https://www.ncbi.nlm.nih.gov/pubmed/36879257
http://dx.doi.org/10.1186/s12894-023-01202-z
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author Yoshida, Soichiro
Takahara, Taro
Arita, Yuki
Ito, Masaya
Hayakawa, Sara
Oguchi, Tomohiko
Komai, Yoshinobu
Numao, Noboru
Yuasa, Takeshi
Inoue, Masaharu
Ushijima, Hiroki
Kudo, Shigehiro
Shimano, Yasumasa
Nakamura, Yuki
Uchida, Yusuke
Uehara, Sho
Tanaka, Hajime
Yaegashi, Hiroshi
Izumi, Kouji
Yokoyama, Minato
Matsuoka, Yoh
Yoshioka, Yasuo
Konishi, Koji
Nakanishi, Katsuyuki
Nagahara, Akira
Hirakawa, Akihiro
Koike, Ryuji
Koga, Fumitaka
Nishimura, Kazuo
Mizokami, Atsushi
Yonese, Junji
Kageyama, Yukio
Yoshimura, Ryoichi
Fujii, Yasuhisa
author_facet Yoshida, Soichiro
Takahara, Taro
Arita, Yuki
Ito, Masaya
Hayakawa, Sara
Oguchi, Tomohiko
Komai, Yoshinobu
Numao, Noboru
Yuasa, Takeshi
Inoue, Masaharu
Ushijima, Hiroki
Kudo, Shigehiro
Shimano, Yasumasa
Nakamura, Yuki
Uchida, Yusuke
Uehara, Sho
Tanaka, Hajime
Yaegashi, Hiroshi
Izumi, Kouji
Yokoyama, Minato
Matsuoka, Yoh
Yoshioka, Yasuo
Konishi, Koji
Nakanishi, Katsuyuki
Nagahara, Akira
Hirakawa, Akihiro
Koike, Ryuji
Koga, Fumitaka
Nishimura, Kazuo
Mizokami, Atsushi
Yonese, Junji
Kageyama, Yukio
Yoshimura, Ryoichi
Fujii, Yasuhisa
author_sort Yoshida, Soichiro
collection PubMed
description BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01202-z.
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spelling pubmed-99870402023-03-07 A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL) Yoshida, Soichiro Takahara, Taro Arita, Yuki Ito, Masaya Hayakawa, Sara Oguchi, Tomohiko Komai, Yoshinobu Numao, Noboru Yuasa, Takeshi Inoue, Masaharu Ushijima, Hiroki Kudo, Shigehiro Shimano, Yasumasa Nakamura, Yuki Uchida, Yusuke Uehara, Sho Tanaka, Hajime Yaegashi, Hiroshi Izumi, Kouji Yokoyama, Minato Matsuoka, Yoh Yoshioka, Yasuo Konishi, Koji Nakanishi, Katsuyuki Nagahara, Akira Hirakawa, Akihiro Koike, Ryuji Koga, Fumitaka Nishimura, Kazuo Mizokami, Atsushi Yonese, Junji Kageyama, Yukio Yoshimura, Ryoichi Fujii, Yasuhisa BMC Urol Study Protocol BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01202-z. BioMed Central 2023-03-06 /pmc/articles/PMC9987040/ /pubmed/36879257 http://dx.doi.org/10.1186/s12894-023-01202-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Yoshida, Soichiro
Takahara, Taro
Arita, Yuki
Ito, Masaya
Hayakawa, Sara
Oguchi, Tomohiko
Komai, Yoshinobu
Numao, Noboru
Yuasa, Takeshi
Inoue, Masaharu
Ushijima, Hiroki
Kudo, Shigehiro
Shimano, Yasumasa
Nakamura, Yuki
Uchida, Yusuke
Uehara, Sho
Tanaka, Hajime
Yaegashi, Hiroshi
Izumi, Kouji
Yokoyama, Minato
Matsuoka, Yoh
Yoshioka, Yasuo
Konishi, Koji
Nakanishi, Katsuyuki
Nagahara, Akira
Hirakawa, Akihiro
Koike, Ryuji
Koga, Fumitaka
Nishimura, Kazuo
Mizokami, Atsushi
Yonese, Junji
Kageyama, Yukio
Yoshimura, Ryoichi
Fujii, Yasuhisa
A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title_full A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title_fullStr A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title_full_unstemmed A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title_short A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)
title_sort phase ii randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (medal)
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987040/
https://www.ncbi.nlm.nih.gov/pubmed/36879257
http://dx.doi.org/10.1186/s12894-023-01202-z
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