Clinical significance of completion of radium-۲۲۳ treatment and acute adverse events in patients with metastatic castration-resistant prostate cancer

Objective(s): In the treatment of castration-resistant prostate cancer (CRPC) with bone metastases, radium-۲۲۳ dichloride (Ra-۲۲۳) is the only bone-targeted drug that shows survival benefits. Completing six courses of Ra-۲۲۳ treatment is thought to be associated with better patient survival, but this treatment has a relatively high rate of acute adverse events. Methods: This retrospective study included ۸۵ patients from ۱۲ institutions in Japan to investigate the clinical significance of the completion of Ra-۲۲۳ treatment and acute adverse events in CRPC patients. Results: Six courses of Ra-۲۲۳ treatment were completed in ۶۵.۹% of the patients. Grade ۳ or higher acute adverse events were observed in ۲۷.۱% of patients. The prostate specific antigen and alkaline phosphatase declined at ۲۶.۹% and ۸۷.۹%, respectively. The overall survival rates at ۱۲ and ۲۴ months were ۸۰.۷% and ۶۳.۲%, respectively. Both completion of six courses of Ra-۲۲۳ treatment and absence of grade ۳ or higher acute adverse events were associated with longer overall survival. In univariate analysis, factors related to the history of treatment (five or more hormone therapy agents and cytotoxic chemotherapy) and hematological parameters (Prostate specific antigen (PSA) doubling time, alkaline phosphatase, hemoglobin, albumin, and serum calcium) were associated with completing six courses of Ra-۲۲۳ treatment without experiencing grade ۳ or higher acute adverse events. Multivariate analysis showed that a history of chemotherapy, PSA doubling time, hemoglobin, and serum calcium showed statistical significance. We built a predictive score by these four factors. Patients with lower scores showed higher rates of treatment success (p<۰.۰۰۱) and longer overall survival (p<۰.۰۰۱) with statistical significance. Conclusions: Accomplishing six courses of Ra-۲۲۳ treatment without grade ۳ or higher acute adverse events was a prognostic factor in patients with mCRPC treated with Ra-۲۲۳. We built a predictive score of treatment success and need future external validation.

Keywords:

radium-۲۲۳ dichloride , Bone metastasis , castration-resistant prostate cancer , radioisotope therapy