Radium-223 in the treatment of metastatic hormone refractory prostate cancer (HRPC): Results from a randomized, placebo-controlled, phase II study

Abstract

5071 Background: The alpha emitter radium-223 is a bone-seeking radionuclide studied as a novel treatment for patients with HRPC and bone metastases. Ra-223 showed minimal toxicity in a phase 1 study (Nilsson S, et al., Clin Cancer Res 2005;11 (12): 4451–59). Here we present outcome data from a randomised phase II study. Methods: Patients with HRPC and bone pain requiring external beam radiotherapy were randomized to treatment with 4 injections of either Ra-223 (50 kBq/kg b.w.) or saline (placebo) every 4 weeks. The primary endpoints were change in bone-alkaline phosphatase (ALP) levels from baseline to 4 weeks after last injection (previously reported (Bruland ØS, et al. Clin Cancer Res 2006;12:6250s-57s), and time to occurrence of Skeletal Related Events (SREs). Secondary endpoints included toxicity, PSA progression and overall survival. Results: 33 patients were randomised to Ra-223 and 31 to placebo. The two groups were well balanced with respect to standard prognostic factors. Mild, transient haematological toxicity was seen after Ra-223. Long term toxicity was not observed. SAEs were observed in 8 patients in the Ra-223 group versus 14 in the placebo group. Based on intention to treat analysis, the median time to PSA progression was 26 versus 8 weeks (p=0.047) for Ra-223 versus placebo, respectively. The median time to first SRE was 28 versus 26 weeks (p= 0.164). The median overall survival was 65.3 weeks versus 46.4 weeks (p = 0.066). The hazard ratio for overall survival, adjusted for baseline PSA, albumin, LDH and performance status was 2.11 (95 % CI: 1.08 - 4.13, p=0.029). At 18 months, 15 (45%) versus 8 (26%) patients patients were still alive. Conclusions: Alpharadin was extremely well tolerated, with minimal myelotoxicity, and with encouraging evidence of efficacy. Larger clinical trials are warranted to study the impact of Alpharadin on the prevention of SREs and on overall survival in HRPC. The bone targeting properties of Alpharadin, may also be applicable to the treatment of skeletal metastasis from other primary cancers. [Table: see text]

Urologists and oncologists: adapting to a new treatment paradigm in castration‐resistant prostate cancer (CRPC)

“…The above discussion is far from comprehensive in describing the multiple molecular pathways implicated in CRPC's complex manifestations and the emerging agents developed to exploit those pathways. In addition to cytotoxic agents; antiandrogen receptor agents; immunotherapies; various additional agents including endothelial receptor antagonists, radium‐223, various tyrosine kinase inhibitors, oestrogens, bisphosphonates, an anti‐clusterin agent (custirsen); and several other classes of immunotherapies as well as various compounds have shown potential efficacy in treating CRPC [35,38,43]. We should state that radium‐223 has now demonstrated overall survival benefit in a randomized phase III trial [44].…”

Metastatic Castrate-Resistant Prostate Cancer: New Landscape, New Challenges

“…The radiopharmaceutical Alpharadin ® has also shown potential in a phase II clinical study [24]. This bone-seeking, alpha-particle emitter is currently undergoing a placebo-controlled, randomised trial in mCRPC [25].…”