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

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• 作者：S. Nilsson^a ; ^l ; ^{Sten.Nilsson@ki.se} ; P. Strang^b ; ^l ; A.K. Aksnes^c ; L. Franzè ; n^d ; ^e ; P. Olivier^f ; A. Pecking^g ; J. Staffurth^h ; S. Vasanthanⁱ ; C. Andersson^j ; Ø ; .S. Bruland^k
• 关键词：Pain ; Bone metastases ; Prostate cancer ; Castration-resistant ; Alpha-pharmaceutical ; Radium ; Alpharadin ; BPI ; Functional index
• 刊名：European Journal of Cancer
• 出版年：2012
• 期刊代码：88_09598049
• 类别：med
• 出版时间：March, 2012
• 卷：48
• 期：5
• 页码：678-686
• 文件大小：512 K

摘要

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 鈭?0, 鈭?1, 鈭?7 and 鈭?8 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.