Table 5.

Summary of clinical trials on the therapeutic efficacy of radium-223 in men with prostate cancer.

Study	Treatment (# patients)	Primary endpoint	Results	Other outcomes	Hematological adverse effects	Comments
Nilsson et al. [90] Phase I	Escalated doses of Ra-223 (25)	Pain relief	At 2 mos, pain relief in 56% patients	Overall survival (OS) 20 mos	Thrombocytopenia grade-1 in 3 pts; leukopenia grade-3 in 3 pts: neutropenia grade-3 in 2 pts	Serum ALP nadir 29.5% in females and 52.1% males
Nilsson et al. [96] Phase II	Ra-223 (31) vs. placebo (33)	Change in ALP concentrations and time to skeletal-related events (SREs)	Change in ALP: 65.6% (Ra-223) vs. 9.3% (placebo), p < 0.0001; HR for time to first SRE 1.75 (0.96–3.19); Time to PSA progression 26 wks (Ra-223) vs. 8 wks (placebo), p = 0.048	OS: 65.3 wks (Ra-223) vs. 46.4 wks (placebo); p = 0.068	Thrombocytopenia grade-3: 0% in Ra-223 vs. 3.03% in placebo; neutropenia grade-2/3: 9.6% in Ra-223 vs. 0% in placebo	–
Parker et al. [98] Phase III (ALSYMPCA trial)	Ra-223 (541) vs. placebo (268)	Overall survival (OS)	OS: 14 mos (Ra-223) vs. 11.2 mos (placebo), HR 0.695, p = 0.001	HR time to total ALP progression: 0.163 (p < 0.00001), HR for time to PSA progression: 0.671 (p = 0.0002),	Anemia grade-3/4 in 11% in Ra-223 vs. 12% in placebo; neutropenia grade-3/4 in 2% in Ra-223 vs. 1% in placebo; thrombocytopenia grade-3/4 in 4% in Ra-223 vs. 2% in placebo	More patients with total ALP response and total ALP normalization in Ra-223 group

Abbreviations: ALP: alkaline phosphatase; HR: hazard ratio; PSA: prostate specific antigen; mos: months; wks: weeks.