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.	中国抗癌协会癌症康复与姑息治疗专业委员会, 中国抗癌协会临床肿瘤学协作专业委员会主编. 恶性肿瘤骨转移及骨相关疾病临床诊疗专家共识 (2014 版). 北京: 北京大学医学出版社, 2014: 1-9.
2.	于世英. 恶性肿瘤骨转移的诊断与治疗 (第二版). 北京: 中国协和医科大学出版社, 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.	蒙荣钦, 李昌林, 朱云芝, 等. 唑来膦酸联合 89Sr 治疗恶性肿瘤晚期多发骨转移疗效观察. 中华实用诊断与治疗杂志, 2013, 27(3): 277-278.
9.	张建国, 王艳丽, 李静. 唑来磷酸联合 89Sr 治疗前列腺癌骨转移. 现代泌尿生殖肿瘤杂志, 2010, 2(5): 213-215.
10.	陈海金, 全亚军, 康建民. 博宁联合 89Sr 治疗肺癌多发骨转移的疗效观察. 山西医科大学学报, 2004, 35(1): 27-28.
11.	白永利, 王林, 董莉. 唑来膦酸钠联合 ⁸⁹SrCl₂ 治疗骨转移瘤的临床疗效. 现代肿瘤医学, 2016, 24(5): 815-818.
12.	李梅, 王火强. ⁸⁹SrCl₂ 联合伊班膦酸钠对肺癌骨转移骨痛的疗效分析. 放射免疫学杂志, 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.	芦亚洲. 放射性核素 89Sr 与唑来磷酸联合治疗乳腺癌多发骨转移的疗效观察. 临床医药文献电子杂志, 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.	张红. 外照射联合 89Sr 内照射治疗转移性骨肿瘤的临床价值. 现代肿瘤医学, 2007, 15(11): 1666-1667.
18.	王卓敏, 李迎春, 任丽, 等. (89)Sr 核素治疗联合椎体成形术或放疗治疗椎体转移癌. 现代肿瘤医学, 2016, 24(4): 643-647.
19.	祝加慧. 联合应用紫杉醇和氯化锶治疗肿瘤骨转移的临床疗效观察. 当代医药论丛, 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.	黄越. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 中国医学工程, 2011, 19(3): 3-4.
22.	李焕斌, 张琦, 王玲, 等. 89Sr 联合内分泌治疗前列腺癌多发骨转移的临床研究. 中国肿瘤, 2009, 18(4): 336-338.
23.	郭德明. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 放射免疫学杂志, 2009, 22(2): 100-102.
24.	常江平, 王风, 史明, 等. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 医师进修杂志•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.	谭忠华, 沈维东, 樊冀伟, 等. 前列腺癌骨转移患者 ⁸⁹SrCl₂ 治疗后血清 E-选择素浓度的变化. 中国肿瘤临床, 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.	孙文伟, 魏丽琴, 谭平, 等. ⁸⁹SrCl₂ 治疗多发性骨转移癌骨痛与 ET、CGRP、TXB₂、6-K-PGF_1a 的关系. 吉林大学学报 (医学版), 2007, 33(3): 581-583.
30.	王洪良, 杨鸿宇, 肖国有, 等. 氯化锶联合局部放疗治疗骨转移瘤的 Meta 分析. 广西医学, 2016, 38(2): 167-170.

1. 中国抗癌协会癌症康复与姑息治疗专业委员会, 中国抗癌协会临床肿瘤学协作专业委员会主编. 恶性肿瘤骨转移及骨相关疾病临床诊疗专家共识 (2014 版). 北京: 北京大学医学出版社, 2014: 1-9.
2. 于世英. 恶性肿瘤骨转移的诊断与治疗 (第二版). 北京: 中国协和医科大学出版社, 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. 蒙荣钦, 李昌林, 朱云芝, 等. 唑来膦酸联合 89Sr 治疗恶性肿瘤晚期多发骨转移疗效观察. 中华实用诊断与治疗杂志, 2013, 27(3): 277-278.
9. 张建国, 王艳丽, 李静. 唑来磷酸联合 89Sr 治疗前列腺癌骨转移. 现代泌尿生殖肿瘤杂志, 2010, 2(5): 213-215.
10. 陈海金, 全亚军, 康建民. 博宁联合 89Sr 治疗肺癌多发骨转移的疗效观察. 山西医科大学学报, 2004, 35(1): 27-28.
11. 白永利, 王林, 董莉. 唑来膦酸钠联合 ⁸⁹SrCl₂ 治疗骨转移瘤的临床疗效. 现代肿瘤医学, 2016, 24(5): 815-818.
12. 李梅, 王火强. ⁸⁹SrCl₂ 联合伊班膦酸钠对肺癌骨转移骨痛的疗效分析. 放射免疫学杂志, 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. 芦亚洲. 放射性核素 89Sr 与唑来磷酸联合治疗乳腺癌多发骨转移的疗效观察. 临床医药文献电子杂志, 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. 张红. 外照射联合 89Sr 内照射治疗转移性骨肿瘤的临床价值. 现代肿瘤医学, 2007, 15(11): 1666-1667.
18. 王卓敏, 李迎春, 任丽, 等. (89)Sr 核素治疗联合椎体成形术或放疗治疗椎体转移癌. 现代肿瘤医学, 2016, 24(4): 643-647.
19. 祝加慧. 联合应用紫杉醇和氯化锶治疗肿瘤骨转移的临床疗效观察. 当代医药论丛, 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. 黄越. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 中国医学工程, 2011, 19(3): 3-4.
22. 李焕斌, 张琦, 王玲, 等. 89Sr 联合内分泌治疗前列腺癌多发骨转移的临床研究. 中国肿瘤, 2009, 18(4): 336-338.
23. 郭德明. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 放射免疫学杂志, 2009, 22(2): 100-102.
24. 常江平, 王风, 史明, 等. 89Sr 联合内分泌疗法治疗前列腺癌骨转移的疗效观察. 医师进修杂志•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. 谭忠华, 沈维东, 樊冀伟, 等. 前列腺癌骨转移患者 ⁸⁹SrCl₂ 治疗后血清 E-选择素浓度的变化. 中国肿瘤临床, 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. 孙文伟, 魏丽琴, 谭平, 等. ⁸⁹SrCl₂ 治疗多发性骨转移癌骨痛与 ET、CGRP、TXB₂、6-K-PGF_1a 的关系. 吉林大学学报 (医学版), 2007, 33(3): 581-583.
30. 王洪良, 杨鸿宇, 肖国有, 等. 氯化锶联合局部放疗治疗骨转移瘤的 Meta 分析. 广西医学, 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