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

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.

• Authors: Hiroji Uemura, Hirotsugu Uemura, Nobuaki Matsubara, Seigo Kinuya, Makoto Hosono, Yoko Yajima, Toshihiko Doi
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 22 Issue 5 Pg. 954-963 (Oct 2017) ISSN: 1437-7772 [Electronic] Japan
• PMID: 28478485 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

• Radioisotopes
• Radiopharmaceuticals
• Alkaline Phosphatase
• Prostate-Specific Antigen
• radium Ra 223 dichloride
• Radium

Topics

• Aged
• Alkaline Phosphatase (blood)
• Anemia (chemically induced)
• Asian People
• Bone Neoplasms (metabolism, secondary)
• Humans
• Male
• Prostate-Specific Antigen
• Prostatic Neoplasms, Castration-Resistant (pathology, radiotherapy)
• Radioisotopes (adverse effects, pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (adverse effects, pharmacokinetics, therapeutic use)
• Radium (adverse effects, pharmacokinetics, therapeutic use)
• Thrombocytopenia (chemically induced)
• Treatment Outcome