Efficacy and safety of <sup>89</sup>SrCl<sub>2</sub> for bone metastases: a meta-analysis _Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Liling ¹ , ZHANG Kaomei ² , YANG Ting ¹ ,  YANG Yanfang ¹ ,  HUANG Min ³

1. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, 610041, P.R.China;
2. Wuxi Center of Disease Control and Prevention, Wuxi, 405800, P.R.China;
3. Chengdu Gaotong Isotope co., LTD, Chengdu, 610041, P.R.China;

Corresponding?author：

YANG Yanfang, Email: yang2009@scu.edu.cn; HUANG Min, Email: huangm113@163.com

Keywords：

Strontium chloride; Bone neoplasm; Neoplasm metastasis; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.201612088

Video：

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ObjectiveTo systematically review the efficacy and safety of ⁸⁹SrCl₂ for bone metastases.MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 12, 2016), MEDLINE, CBM, VIP, CNKI and WanFang Data were electronically searched from inception to December 2016 to collect randomized controlled trials (RCT) about ⁸⁹SrCl₂ in the treatment of bone metastases. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 19 RCTs involving 1 899 patients were included. The results of meta-analysis showed that: compared to the group without ⁸⁹SrCl₂, group of ⁸⁹SrCl₂ combined with other treatments had benefits for complete relief of bone pain (RR=1.53, 95%CI 1.16 to 2.01, P=0.002), total relief of bone pain (RR=1.33, 95%CI 1.22 to 1.45, P<0.001), bone metastases complete response rate (RR=1.61, 95%CI 1.20 to 2.16, P=0.002), bone metastases total response rate (RR=1.61, 95%CI 1.26 to 2.08, P<0.001), improvement of quality of life (RR=1.44, 95%CI 1.06 to 1.97, P=0.02). The proportion of pain flare (RR=10.35, 95%CI 2.01 to 53.37, P=0.005), leucopenia (RR=2.49, 95%CI 1.84 to 3.37, P<0.001) and thrombocytopenia (RR=2.64, 95%CI 1.76 to 3.97, P<0.001) in the ⁸⁹SrCl₂ group were higher than that in the control group.Conclusion⁸⁹SrCl₂ combined with the other treatments is better for bone metastases than without ⁸⁹SrCl₂. Due to the limited quantity and quality of included studies, the above results should be verify by more high quality studies.

Citation： CHEN Liling, ZHANG Kaomei, YANG Ting, YANG Yanfang, HUANG Min. Efficacy and safety of ⁸⁹SrCl₂ for bone metastases: a meta-analysis . Chinese Journal of Evidence-Based Medicine, 2017, 17(9): 1043-1050. doi: 10.7507/1672-2531.201612088 Copy

1.	中國抗癌協會癌癥康復與姑息治療專業委員會, 中國抗癌協會臨床腫瘤學協作專業委員會主編. 惡性腫瘤骨轉移及骨相關疾病臨床診療專家共識 (2014 版). 北京: 北京大學醫學出版社, 2014: 1-9.
2.	于世英. 惡性腫瘤骨轉移的診斷與治療 (第二版). 北京: 中國協和醫科大學出版社, 2012: 117.
3.	Furubayashi N, Negishi T, Ura S, et al. Palliative effects and adverse events of strontium 89 for prostate cancer patients with bone metastasis. Mol Clin Oncol, 2015, 3(1): 257-263.
4.	Heianna J, Toita T, Endo W, et al. Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience. Ann Nucl Med, 2015, 29(10): 848-853.
5.	Zenda S, Nakagami Y, Toshima M, et al. Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases. Int J Clin Oncol, 2014, 19(4): 739-743.
6.	Yamada K, Kaise H, Komatsu S, et al. Abstract C216: The safety and efficacy of the concurrent use of radiopharmaceutical strontium-89 (Sr-89) chloride with zoledronic acid in standard anticancer therapy for breast cancer patients with painful multifocal bone metastases. Mol Cancer Ther, 2013, 12(11 Suppl): C216.
7.	Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available at: www.cochranehandbook.org.
8.	蒙榮欽, 李昌林, 朱云芝, 等. 唑來膦酸聯合 89Sr 治療惡性腫瘤晚期多發骨轉移療效觀察. 中華實用診斷與治療雜志, 2013, 27(3): 277-278.
9.	張建國, 王艷麗, 李靜. 唑來磷酸聯合 89Sr 治療前列腺癌骨轉移. 現代泌尿生殖腫瘤雜志, 2010, 2(5): 213-215.
10.	陳海金, 全亞軍, 康建民. 博寧聯合 89Sr 治療肺癌多發骨轉移的療效觀察. 山西醫科大學學報, 2004, 35(1): 27-28.
11.	白永利, 王林, 董莉. 唑來膦酸鈉聯合 ⁸⁹SrCl₂ 治療骨轉移瘤的臨床療效. 現代腫瘤醫學, 2016, 24(5): 815-818.
12.	李梅, 王火強. ⁸⁹SrCl₂ 聯合伊班膦酸鈉對肺癌骨轉移骨痛的療效分析. 放射免疫學雜志, 2013, 26(4): 390-392.
13.	Wang Y, Tao H, Yu X, et al. Clinical significance of zoledronic acid and strontium-89 in patients with asymptomatic bone metastases from non-small-cell lung cancer. Clin Lung Cancer, 2013, 14(3): 254-260.
14.	蘆亞洲. 放射性核素 89Sr 與唑來磷酸聯合治療乳腺癌多發骨轉移的療效觀察. 臨床醫藥文獻電子雜志, 2016, 3(20): 3954-3955.
15.	Smeland S, Erikstein B, Aas M, et al. Role of strontium-89 as adjuvant to palliative external beam radiotherapy is questionable: results of a double-blind randomized study. Int J Radiat Oncol Biol Phys, 2003, 56(5): 1397-1404.
16.	Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys, 1993, 25(5): 805-813.
17.	張紅. 外照射聯合 89Sr 內照射治療轉移性骨腫瘤的臨床價值. 現代腫瘤醫學, 2007, 15(11): 1666-1667.
18.	王卓敏, 李迎春, 任麗, 等. (89)Sr 核素治療聯合椎體成形術或放療治療椎體轉移癌. 現代腫瘤醫學, 2016, 24(4): 643-647.
19.	祝加慧. 聯合應用紫杉醇和氯化鍶治療腫瘤骨轉移的臨床療效觀察. 當代醫藥論叢, 2014, 12(5): 135-136.
20.	Tu SM, Millikan RE, Menqistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomized phase II trial. Lancet, 2001, 357(9253): 336-341.
21.	黃越. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 中國醫學工程, 2011, 19(3): 3-4.
22.	李煥斌, 張琦, 王玲, 等. 89Sr 聯合內分泌治療前列腺癌多發骨轉移的臨床研究. 中國腫瘤, 2009, 18(4): 336-338.
23.	郭德明. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 放射免疫學雜志, 2009, 22(2): 100-102.
24.	常江平, 王風, 史明, 等. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 醫師進修雜志?外科版, 2005, 28(4): 28-29.
25.	Bilen MA, Johnson MM, Mathew P, et al. Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer. Cancer, 2015, 121(1): 69-76.
26.	James ND, Pirrie SJ, Pope AM, et al. Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both: the TRAPEZE randomized clinical trial. JAMA Oncol, 2016, 2(4): 493-499.
27.	譚忠華, 沈維東, 樊冀偉, 等. 前列腺癌骨轉移患者 ⁸⁹SrCl₂ 治療后血清 E-選擇素濃度的變化. 中國腫瘤臨床, 2005, 32(20): 1177-1179.
28.	Davis J, Pither RJ. Biochemical responses in cultured cells following exposure to (89)SrCl(2): potential relevance to the mechanism of action in pain palliation. Eur J Cancer, 2001, 37(18): 2464-2469.
29.	孫文偉, 魏麗琴, 譚平, 等. ⁸⁹SrCl₂ 治療多發性骨轉移癌骨痛與 ET、CGRP、TXB₂、6-K-PGF_1a 的關系. 吉林大學學報 (醫學版), 2007, 33(3): 581-583.
30.	王洪良, 楊鴻宇, 肖國有, 等. 氯化鍶聯合局部放療治療骨轉移瘤的 Meta 分析. 廣西醫學, 2016, 38(2): 167-170.

1. 中國抗癌協會癌癥康復與姑息治療專業委員會, 中國抗癌協會臨床腫瘤學協作專業委員會主編. 惡性腫瘤骨轉移及骨相關疾病臨床診療專家共識 (2014 版). 北京: 北京大學醫學出版社, 2014: 1-9.
2. 于世英. 惡性腫瘤骨轉移的診斷與治療 (第二版). 北京: 中國協和醫科大學出版社, 2012: 117.
3. Furubayashi N, Negishi T, Ura S, et al. Palliative effects and adverse events of strontium 89 for prostate cancer patients with bone metastasis. Mol Clin Oncol, 2015, 3(1): 257-263.
4. Heianna J, Toita T, Endo W, et al. Concurrent use of strontium-89 with external beam radiotherapy for multiple bone metastases: early experience. Ann Nucl Med, 2015, 29(10): 848-853.
5. Zenda S, Nakagami Y, Toshima M, et al. Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with multiple bone metastases. Int J Clin Oncol, 2014, 19(4): 739-743.
6. Yamada K, Kaise H, Komatsu S, et al. Abstract C216: The safety and efficacy of the concurrent use of radiopharmaceutical strontium-89 (Sr-89) chloride with zoledronic acid in standard anticancer therapy for breast cancer patients with painful multifocal bone metastases. Mol Cancer Ther, 2013, 12(11 Suppl): C216.
7. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available at: www.cochranehandbook.org.
8. 蒙榮欽, 李昌林, 朱云芝, 等. 唑來膦酸聯合 89Sr 治療惡性腫瘤晚期多發骨轉移療效觀察. 中華實用診斷與治療雜志, 2013, 27(3): 277-278.
9. 張建國, 王艷麗, 李靜. 唑來磷酸聯合 89Sr 治療前列腺癌骨轉移. 現代泌尿生殖腫瘤雜志, 2010, 2(5): 213-215.
10. 陳海金, 全亞軍, 康建民. 博寧聯合 89Sr 治療肺癌多發骨轉移的療效觀察. 山西醫科大學學報, 2004, 35(1): 27-28.
11. 白永利, 王林, 董莉. 唑來膦酸鈉聯合 ⁸⁹SrCl₂ 治療骨轉移瘤的臨床療效. 現代腫瘤醫學, 2016, 24(5): 815-818.
12. 李梅, 王火強. ⁸⁹SrCl₂ 聯合伊班膦酸鈉對肺癌骨轉移骨痛的療效分析. 放射免疫學雜志, 2013, 26(4): 390-392.
13. Wang Y, Tao H, Yu X, et al. Clinical significance of zoledronic acid and strontium-89 in patients with asymptomatic bone metastases from non-small-cell lung cancer. Clin Lung Cancer, 2013, 14(3): 254-260.
14. 蘆亞洲. 放射性核素 89Sr 與唑來磷酸聯合治療乳腺癌多發骨轉移的療效觀察. 臨床醫藥文獻電子雜志, 2016, 3(20): 3954-3955.
15. Smeland S, Erikstein B, Aas M, et al. Role of strontium-89 as adjuvant to palliative external beam radiotherapy is questionable: results of a double-blind randomized study. Int J Radiat Oncol Biol Phys, 2003, 56(5): 1397-1404.
16. Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys, 1993, 25(5): 805-813.
17. 張紅. 外照射聯合 89Sr 內照射治療轉移性骨腫瘤的臨床價值. 現代腫瘤醫學, 2007, 15(11): 1666-1667.
18. 王卓敏, 李迎春, 任麗, 等. (89)Sr 核素治療聯合椎體成形術或放療治療椎體轉移癌. 現代腫瘤醫學, 2016, 24(4): 643-647.
19. 祝加慧. 聯合應用紫杉醇和氯化鍶治療腫瘤骨轉移的臨床療效觀察. 當代醫藥論叢, 2014, 12(5): 135-136.
20. Tu SM, Millikan RE, Menqistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomized phase II trial. Lancet, 2001, 357(9253): 336-341.
21. 黃越. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 中國醫學工程, 2011, 19(3): 3-4.
22. 李煥斌, 張琦, 王玲, 等. 89Sr 聯合內分泌治療前列腺癌多發骨轉移的臨床研究. 中國腫瘤, 2009, 18(4): 336-338.
23. 郭德明. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 放射免疫學雜志, 2009, 22(2): 100-102.
24. 常江平, 王風, 史明, 等. 89Sr 聯合內分泌療法治療前列腺癌骨轉移的療效觀察. 醫師進修雜志?外科版, 2005, 28(4): 28-29.
25. Bilen MA, Johnson MM, Mathew P, et al. Randomized phase 2 study of bone-targeted therapy containing strontium-89 in advanced castrate-sensitive prostate cancer. Cancer, 2015, 121(1): 69-76.
26. James ND, Pirrie SJ, Pope AM, et al. Clinical outcomes and survival following treatment of metastatic castrate-refractory prostate cancer with docetaxel alone or with strontium-89, zoledronic acid, or both: the TRAPEZE randomized clinical trial. JAMA Oncol, 2016, 2(4): 493-499.
27. 譚忠華, 沈維東, 樊冀偉, 等. 前列腺癌骨轉移患者 ⁸⁹SrCl₂ 治療后血清 E-選擇素濃度的變化. 中國腫瘤臨床, 2005, 32(20): 1177-1179.
28. Davis J, Pither RJ. Biochemical responses in cultured cells following exposure to (89)SrCl(2): potential relevance to the mechanism of action in pain palliation. Eur J Cancer, 2001, 37(18): 2464-2469.
29. 孫文偉, 魏麗琴, 譚平, 等. ⁸⁹SrCl₂ 治療多發性骨轉移癌骨痛與 ET、CGRP、TXB₂、6-K-PGF_1a 的關系. 吉林大學學報 (醫學版), 2007, 33(3): 581-583.
30. 王洪良, 楊鴻宇, 肖國有, 等. 氯化鍶聯合局部放療治療骨轉移瘤的 Meta 分析. 廣西醫學, 2016, 38(2): 167-170.

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Chinese Journal of Evidence-Based Medicine

Efficacy and safety of ⁸⁹SrCl₂ for bone metastases: a meta-analysis

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Chinese Journal of Evidence-Based Medicine

Efficacy and safety of 89SrCl2 for bone metastases: a meta-analysis

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Efficacy and safety of ⁸⁹SrCl₂ for bone metastases: a meta-analysis