A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer
2012 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no 5, 678-686 p.Article, review/survey (Refereed) Published
Purpose: To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical.
Methods: One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 kBq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders.
Results: A significant dose response for pain index was seen at week 2 (P = .035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 kBq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P = .008, P = .0005, P = .002, and P < .0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P = .04, .01, .002 and .02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P = .0067). All doses were safe and well tolerated.
Conclusion: Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed. (C) 2012 Elsevier Ltd. All rights reserved.
Place, publisher, year, edition, pages
Oxford: Elsevier, 2012. Vol. 48, no 5, 678-686 p.
Pain, Bone metastases, Prostate cancer, Castration-resistant, Alpha-pharmaceutical, Radium, Alpharadin, BPI, Functional index
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-54130DOI: 10.1016/j.ejca.2011.12.023ISI: 000301849900007OAI: oai:DiVA.org:umu-54130DiVA: diva2:517347