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International Journal of Clinical Oncology

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Open Access 01-10-2017 | Original Article

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

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

Published in: International Journal of Clinical Oncology | Issue 5/2017

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.

The Japanese Society of Nuclear Medicine (NA) manual for proper use in clinical trials relating to radionuclide therapy with radium-223 dichloride (Ra-223) injection.

The Japanese Society of Nuclear Medicine (NA) Addendum to the manual for proper use in clinical trials relating to radionuclide therapy with Ra-223 dichloride (Ra-223) injection: methods of calculating radiation shielding and levels of radioactivity in the atmosphere, exhaust air and exhaust fluid.

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Title: Safety and efficacy of radium-223 dichloride in Japanese patients with castration-resistant prostate cancer and bone metastases
Authors: Hiroji Uemura
Hirotsugu Uemura
Nobuaki Matsubara
Seigo Kinuya
Makoto Hosono
Yoko Yajima
Toshihiko Doi
Publication date: 01-10-2017
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 5/2017
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-017-1130-1

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