Phase II Study of radium-223 Dichloride in Japanese Patients With Symptomatic Castration-Resistant Prostate Cancer

Int J Clin Oncol. 2018 Feb;23(1):173-180. doi: 10.1007/s10147-017-1176-0. Epub 2017 Aug 2.

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.

Keywords: Alkaline phosphatase; Bone metastasis; Castration-resistant prostate cancer; Prostate-specific antigen; Radium-223 dichloride.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Humans
  • Lymphocyte Count
  • Male
  • Prostate-Specific Antigen / analysis
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radioisotopes / adverse effects
  • Radioisotopes / therapeutic use
  • Radium / adverse effects*
  • Radium / therapeutic use*
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01929655