A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer - Abstract

BACKGROUND: Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile.

OBJECTIVE: To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases.

DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the proportion of patients in each dose group who had a confirmed decrease of ≥50% in baseline prostate-specific antigen (PSA) levels.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups.

RESULTS AND LIMITATIONS: The study met its primary end point with a statistically significant dose-response relationship in confirmed ≥50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p=0.0297). A ≥50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p< 0.0001). The most common treatment-related AEs (≥10%) occurring up to week 24 across all dose groups were diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic events was seen among dose groups. Potential limitations include small patient numbers and differences among dose groups at baseline.

CONCLUSIONS: Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223 was well tolerated at all doses.

Written by:
Parker CC, Pascoe S, Chodacki A, O'Sullivan JM, Germá JR, O'Bryan-Tear CG, Haider T, Hoskin P.   Are you the author?
Royal Marsden Hospital, Sutton, UK.

Reference: Eur Urol. 2012 Sep 13. pii: S0302-2838(12)01031-7.
doi: 10.1016/j.eururo.2012.09.008

PubMed Abstract
PMID: 23000088

UroToday.com Prostate Cancer Section