Safety and efficacy of radium-223 dichloride in Japanese patients with castration-resistant prostate cancer and bone metastases

Hiroji Uemura, Hirotsugu Uemura, Nobuaki Matsubara, Seigo Kinuya, Makoto Hosono, Yoko Yajima, Toshihiko Doi, Hiroji Uemura, Hirotsugu Uemura, Nobuaki Matsubara, Seigo Kinuya, Makoto Hosono, Yoko Yajima, Toshihiko Doi

Abstract

Background: Radiation therapy with radium-223 dichloride improves overall survival, reduces symptomatic skeletal events in Caucasian patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is well tolerated. We report here the results of the first efficacy and safety study of radium-223 dichloride in a Japanese population.

Methods: In this open-label, uncontrolled, non-randomized, phase I trial, radium-223 dichloride was given to Japanese patients with CRPC and ≥2 bone metastases in 4-week cycles. The patients were divided into three cohorts, with cohort 1 and the expansion cohort receiving injections of radium-223 dichloride [55 kBq/kg body weight (BW)] every 4 weeks (Q4W) for up to six injections, and cohort 2 receiving an initial single radium-223 dichloride injection of 110 kBq/kg BW followed by up to five injections of 55 kBq/kg BW Q4W. Safety was determined via adverse event (AE) reporting, and biochemical bone markers were assessed for treatment efficacy.

Results: In total 19 patients received at least one dose of radium-223 dichloride and 18 patients experienced at least one treatment-emergent AE (TEAE) of which the most common were anemia, thrombocytopenia, and lymphocytopenia. Serious AEs were reported in three patients but none were drug-related. In the patients of cohort 1 + expansion cohort (55 kBq/kg BW Q4W treatment; n = 16), prostate-specific antigen levels remained stable or slightly increased while the bone alkaline phosphatase (ALP) level significantly decreased. The response rates of bone ALP (≥30 and ≥50% reductions) were 81.8 and 36.4% at week 12, and 81.3 and 50.0% at the end of treatment.

Conclusions: Radium-223 dichloride was well tolerated in these Japanese patients and, at a dose of 55 kBq/kg BW, efficacy on biomarkers was as expected. The outcomes in Japanese patients were consistent with those reported in other non-Japanese populations.

Trial registration: ClinicalTrials.gov record NCT01565746.

Keywords: Castration-resistant prostate cancer; Efficacy; Japanese patients; Radium-223 dichloride; Safety.

Conflict of interest statement

Seigo Kinuya received lecture fees from Bayer, Japan. Yoko Yajima is an employee of Bayer Yakuhin, Ltd. Hiroji Uemura, Hirotsugu Uemura, Nobuaki Matsubara, Makoto Hosono and Toshihiko Doi have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Percentage changes from baseline in prostate-specific antigen (PSA) levels after treatment with radium-223 dichloride at 50 kBq/kg (cohort 1 + expansion cohort, n = 16). Filled circles Mean ± standard deviation (SD). EOT End of treatment. PSA response rate was defined as the percentage of patients whose PSA blood level was reduced by ≥30 or ≥50% vs. baseline
Fig. 2
Fig. 2
Percentage changes from baseline in total alkaline phosphatase (ALP) levels after treatment with radium-223 dichloride at 50 kBq/kg (cohort 1 + expansion cohort, n = 16). Filled circles Mean ± SD. ALP response rate was defined as the percentage of subjects whose ALP blood level was reduced by ≥30 or ≥50% vs. baseline
Fig. 3
Fig. 3
Percentage changes from baseline in bone ALP levels after treatment with radium-223 dichloride at 50 kBq/kg (cohort 1 + expansion cohort, n = 16). Filled circles mean ± SD. ALP response rate was defined as the percentage of subjects whose ALP blood level was reduced by ≥30 or ≥50% vs. baseline

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