Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer

Nobuaki Matsubara, Satsohi Nagamori, Yoshiaki Wakumoto, Hirotsugu Uemura, Go Kimura, Akira Yokomizo, Hiroaki Kikukawa, Atsushi Mizokami, Takeo Kosaka, Naoya Masumori, Yoshihide Kawasaki, Junji Yonese, Yasutomo Nasu, Satoshi Fukasawa, Takayuki Sugiyama, Seigo Kinuya, Makoto Hosono, Iku Yamaguchi, Hirokazu Tsutsui, Hiroji Uemura

Research output: Contribution to journalArticle

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Abstract

Background: Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases. Methods: In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period. Results: Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was −19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%). Conclusions: Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. Clinical trial registration: ClinicalTrials.gov NCT01929655.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalInternational Journal of Clinical Oncology
DOIs
Publication statusAccepted/In press - Aug 2 2017

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Radium
Castration
Bone Neoplasms
Prostatic Neoplasms
Alkaline Phosphatase
Prostate-Specific Antigen
Neoplasm Metastasis
Therapeutics
Lymphocyte Count
Anorexia
Anemia
Survival Rate
Clinical Trials
Safety
Bone and Bones
Pain
Survival

Keywords

  • Alkaline phosphatase
  • Bone metastasis
  • Castration-resistant prostate cancer
  • Prostate-specific antigen
  • Radium-223 dichloride

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

Cite this

Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer. / Matsubara, Nobuaki; Nagamori, Satsohi; Wakumoto, Yoshiaki; Uemura, Hirotsugu; Kimura, Go; Yokomizo, Akira; Kikukawa, Hiroaki; Mizokami, Atsushi; Kosaka, Takeo; Masumori, Naoya; Kawasaki, Yoshihide; Yonese, Junji; Nasu, Yasutomo; Fukasawa, Satoshi; Sugiyama, Takayuki; Kinuya, Seigo; Hosono, Makoto; Yamaguchi, Iku; Tsutsui, Hirokazu; Uemura, Hiroji.

In: International Journal of Clinical Oncology, 02.08.2017, p. 1-8.

Research output: Contribution to journalArticle

Matsubara, N, Nagamori, S, Wakumoto, Y, Uemura, H, Kimura, G, Yokomizo, A, Kikukawa, H, Mizokami, A, Kosaka, T, Masumori, N, Kawasaki, Y, Yonese, J, Nasu, Y, Fukasawa, S, Sugiyama, T, Kinuya, S, Hosono, M, Yamaguchi, I, Tsutsui, H & Uemura, H 2017, 'Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer', International Journal of Clinical Oncology, pp. 1-8. https://doi.org/10.1007/s10147-017-1176-0
Matsubara, Nobuaki ; Nagamori, Satsohi ; Wakumoto, Yoshiaki ; Uemura, Hirotsugu ; Kimura, Go ; Yokomizo, Akira ; Kikukawa, Hiroaki ; Mizokami, Atsushi ; Kosaka, Takeo ; Masumori, Naoya ; Kawasaki, Yoshihide ; Yonese, Junji ; Nasu, Yasutomo ; Fukasawa, Satoshi ; Sugiyama, Takayuki ; Kinuya, Seigo ; Hosono, Makoto ; Yamaguchi, Iku ; Tsutsui, Hirokazu ; Uemura, Hiroji. / Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer. In: International Journal of Clinical Oncology. 2017 ; pp. 1-8.
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abstract = "Background: Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases. Methods: In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period. Results: Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was −19.3 and +97.4{\%}, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89{\%}, respectively. The ALP response rate was 31{\%}, while the PSA response rate was 6{\%}. Grade 3/4 treatment-emergent adverse events observed in ≥10{\%} of patients included decreased lymphocyte count (14{\%}), anemia (14{\%}), anorexia (10{\%}), and bone pain (10{\%}). Conclusions: Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. Clinical trial registration: ClinicalTrials.gov NCT01929655.",
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T1 - Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer

AU - Matsubara, Nobuaki

AU - Nagamori, Satsohi

AU - Wakumoto, Yoshiaki

AU - Uemura, Hirotsugu

AU - Kimura, Go

AU - Yokomizo, Akira

AU - Kikukawa, Hiroaki

AU - Mizokami, Atsushi

AU - Kosaka, Takeo

AU - Masumori, Naoya

AU - Kawasaki, Yoshihide

AU - Yonese, Junji

AU - Nasu, Yasutomo

AU - Fukasawa, Satoshi

AU - Sugiyama, Takayuki

AU - Kinuya, Seigo

AU - Hosono, Makoto

AU - Yamaguchi, Iku

AU - Tsutsui, Hirokazu

AU - Uemura, Hiroji

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N2 - Background: Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases. Methods: In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period. Results: Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was −19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%). Conclusions: Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. Clinical trial registration: ClinicalTrials.gov NCT01929655.

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KW - Prostate-specific antigen

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