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转移性骨肿瘤及其引发的骨骼相关事件是造成很多晚期恶性肿瘤患者生活质量下降甚至死亡的重要原因。虽然现代医学较为发达,但目前转移性骨肿瘤的治疗仍然是临床工作中的难点。治疗转移性骨肿瘤的方法主要有骨吸收抑制剂治疗、放射性药物治疗、放疗、手术治疗以及中医治疗等。氯化锶[89Sr](以下简称“89Sr”)是目前临床上使用较多的一种治疗恶性转移性骨肿瘤的放射性药物,其可以使50%~90%的转移性骨肿瘤患者的疼痛得到部分缓解,12%~33%的转移性骨肿瘤患者的疼痛得到完全缓解;89Sr发射的β射线的最高射线能量为1.495 MeV,平均射线能量为0.58 MeV,平均软组织穿透射程为2.4 mm,89Sr发射的射线中仅有0.00956%的γ射线,其能量峰值为0.91 MeV[1]。89Sr在生物体内的代谢方式与钙类似,经静脉注入人体后,89Sr会聚集于骨代谢活跃的位置,其在骨转移灶中的浓度明显高于周围正常骨(为正常骨的2~25倍);89Sr的物理半衰期为50.5 d,生物半衰期为4~5 d[2]。Das和Banerjee[3]研究发现,静脉注射89Sr后第90天,89Sr在骨转移灶中的活度仍为注射时的20%,因此89Sr的疗效维持时间可达4~15个月;89Sr的给药剂量一般为1.5~2.2 MBq/kg(40~60 µCi/kg)或148 MBq(4 mCi),在给药2~4周后起效。89Sr治疗的早期不良反应为闪烁现象,即经静脉注射89Sr后,患者的疼痛症状加剧,发生率为10%,一般发生在注射89Sr后的72 h内,通常闪烁现象的发生提示预后良好;89Sr治疗的最主要的晚期不良反应为骨髓抑制,多数可以在3个月内恢复,不可逆的骨髓抑制极为罕见[1]。在临床工作中,由于一些临床医师对放射性药物治疗缺乏了解,担心其会引起严重的骨髓抑制,因此,放射性药物治疗常被临床医师忽视或仅作为其他治疗方法无效时的备选治疗方案。我们结合国内外的相关文献报道,对89Sr治疗转移性骨肿瘤过程中引起骨髓抑制的相关因素进行综述,以指导临床医师用药。
氯化锶[89Sr]治疗转移性骨肿瘤致骨髓抑制的相关因素
Related factors of myelosuppression induced by strontium-89 chloride treatment of bone metastases
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摘要: 氯化锶[89Sr](以下简称“89Sr”)是一种治疗转移性骨肿瘤尤其是全身多发性转移性骨肿瘤的放射性药物,但89Sr致骨髓抑制的不良反应使其临床应用受到了一定的限制。除了89Sr本身的放射生物效应外,89Sr治疗时的骨肿瘤负荷,89Sr治疗前的放疗、化疗以及抗雄激素治疗等都是引起骨髓抑制的重要因素。笔者对89Sr治疗转移性骨肿瘤致骨髓抑制的相关因素进行综述。Abstract: Strontium-89 chloride (hereinafter referred to as "89Sr") is a radiopharmaceutical for the treatment of bone metastases, especially systemic multiple bone metastases, but its clinical application is limited due to the adverse effect of myelosuppression. In addition to the radiobiological effects of 89Sr itself, bone tumor burden during 89Sr treatment, radiotherapy, chemotherapy and anti-androgen therapy before 89Sr treatment are all important factors leading to myelosuppression. The authors review the related factors of myelosuppression induced by 89Sr treatment of bone metastases.
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Key words:
- Strontium radioisotopes /
- Bone neoplasms /
- Neoplasm metastasis /
- Myelosuppression
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[1] Handkiewicz-Junak D, Poeppel TD, Bodei L, et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides[J]. Eur J Nucl Med Mol Imaging, 2018, 45(5): 846−859. DOI: 10.1007/s00259-018-3947-x. [2] 李少林, 王荣福, 张永学, 等. 核医学[M]. 8版. 北京: 人民卫生出版社, 2013: 309.
Li SL, Wang RF, Zhang YX, et al. Nuclear medicine[M]. 8th ed. Beijing: People's Medical Publishing House, 2013: 309.[3] Das T, Banerjee S. Radiopharmaceuticals for metastatic bone pain palliation: available options in the clinical domain and their comparisons[J]. Clin Exp Metastasis, 2017, 34(1): 1−10. DOI: 10.1007/s10585-016-9831-9. [4] Giammarile F, Mognetti T, Resche I. Bone pain palliation with strontium-89 in cancer patients with bone metastases[J]. Q J Nucl Med, 2001, 45(1): 78−83. [5] 中华医学会核医学分会转移性骨肿瘤治疗工作委员会. 氯化锶[89Sr]治疗转移性骨肿瘤专家共识(2017年版)[J]. 中华核医学与分子影像杂志, 2018, 38(6): 412−415. DOI: 10.3760/cma.j.issn.2095-2848.2018.06.008.
The Chinese Society of Nuclear Medicine Working Committee for Treatment of Bone Metastasis. Expert consensus on strontium-89 chloride treatment of bone metastases (2017)[J]. Chin J Nucl Med Mol Imaging, 2018, 38(6): 412−415. DOI: 10.3760/cma.j.issn.2095-2848.2018.06.008.[6] 姜少军, 谢克基, 蔡岳斌, 等. 前列腺癌骨转移对造血功能的影响[J]. 中国医师进修杂志, 2007, 30(20): 27−28. DOI: 10.3760/cma.j.issn.1673-4904.2007.20.010.
Jiang SJ, Xie KJ, Cai YB, et al. Influence of prostatic carcinoma osseous metastasis on the haematogenesis function[J]. Chin J Postgrad Med, 2007, 30(20): 27−28. DOI: 10.3760/cma.j.issn.1673-4904.2007.20.010.[7] Furubayashi N, Negishi T, Ura S, et al. Palliative effects and adverse events of strontium-89 for prostate cancer patients with bone metastasis[J]. Mol Clin Oncol, 2015, 3(1): 257−263. DOI: 10.3892/mco.2014.449. [8] Soloway MS, Hardeman SW, Hickey D, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan[J]. Cancer, 1988, 61(1): 195−202. DOI: 10.1002/1097-0142(19880101)61:1<195::aid-cncr2820610133>3.0.co;2-y. [9] 梁树君, 朱广文, 周绍军, 等. SPECT骨显像联合血清碱性磷酸酶检测评估肺癌患者骨转移负荷的价值[J]. 现代肿瘤医学, 2017, 25(13): 2140−2143. DOI: 10.3969/j.issn.1672-4992.2017.13.033.
Liang SJ, Zhu GW, Zhou SJ, et al. Evaluate of the value of bone metastases burden by SPECT bone imaging combined with serums alkaline phosphalase in patients with lung cancer[J]. J Mod Oncol, 2017, 25(13): 2140−2143. DOI: 10.3969/j.issn.1672-4992.2017.13.033.[10] 琚建军, 李云, 郑军荣, 等. 血清碱性磷酸酶在去势抵抗性前列腺癌伴骨转移化疗中的临床意义[J]. 现代医学, 2019, 47(8): 966−969. DOI: 10.3969/j.issn.1671-7562.2019.08.017.
Ju JJ, Li Y, Zheng JR, et al. Clinical significance of serum alkaline phosphatase in castration-resistant prostate cancer with chemotherapy for bone metastasis[J]. Mod Med J, 2019, 47(8): 966−969. DOI: 10.3969/j.issn.1671-7562.2019.08.017.[11] Leeming DJ, Koizumi M, Byrjalsen I, et al. The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients[J]. Cancer Epidemiol Biomarkers Prev, 2006, 15(1): 32−38. DOI: 10.1158/1055-9965.EPI-05-0492. [12] Bayrak SB, Ceylan E, Serter M, et al. The clinical importance of bone metabolic markers in detecting bone metastasis of lung cancer[J]. Int J Clin Oncol, 2012, 17(2): 112−118. DOI: 10.1007/s10147-011-0266-7. [13] 王晶晶, 刘琛, 秦艳茹. 血清碱性磷酸酶、癌胚抗原、糖类抗原19-9联合检测对胃癌骨转移的诊断价值[J]. 癌症进展, 2020, 18(7): 731−734. DOI: 10.11877/j.issn.1672-1535.2020.18.07.23.
Wang JJ, Liu C, Qin YR, et al. Diagnostic value of combined detection of serum alkaline phosphatase, carcinoem-bryonic antigen and carbohydrate antigen 19-9 in patients with bone metastasis of gastric cancer[J]. Oncol Prog, 2020, 18(7): 731−734. DOI: 10.11877/j.issn.1672-1535.2020.18.07.23.[14] Karhade AV, Thio QCBS, Kuverji M, et al. Prognostic value of serum alkaline phosphatase in spinal metastatic disease[J]. Br J Cancer, 2019, 120(6): 640−646. DOI: 10.1038/s41416-019-0407-8. [15] 胡群超, 俞晓立. 放疗在乳腺癌骨转移中的临床应用进展[J]. 中国癌症杂志, 2016, 26(4): 346−350. DOI: 10.3969/j.issn.1007-3969.2016.04.010.
Hu QC, Yu XL. Progress in the clinical use of radiotherapy for bone metastasis in breast cancer[J]. China Oncol, 2016, 26(4): 346−350. DOI: 10.3969/j.issn.1007-3969.2016.04.010.[16] 黄伟, 钱梦, 谢鸣. 肿瘤放射治疗配合中药增效减毒的临床研究进展[J]. 中国药师, 2017, 20(8): 1374−1381. DOI: 10.3969/j.issn.1008-049X.2017.08.011.
Huang W, Qian M, Xie M. Clinical study progress in tumor radiotherapy combined with traditional Chinese medicines with synergistic and attenuated effects[J]. China Pharm, 2017, 20(8): 1374−1381. DOI: 10.3969/j.issn.1008-049X.2017.08.011.[17] Meng AM, Wang Y, Brown SA, et al. Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apoptosis-dependent and -independent mechanisms[J]. Exp Hematol, 2003, 31(12): 1348−1356. DOI: 10.1016/j.exphem.2003.08.014. [18] 刘慧云, 刘东胜. 不同分割方式放疗治疗骨转移肿瘤的临床疗效[J]. 肿瘤基础与临床, 2020, 33(2): 107−109. DOI: 10.3969/j.issn.1673-5412.2020.02.004.
Liu HY, Liu DS. Clinical efficacy of radiotherapy with different segmentation methods in the treatment of bone metastases[J]. J Basic Clin Oncol, 2020, 33(2): 107−109. DOI: 10.3969/j.issn.1673-5412.2020.02.004.[19] 左二冬. 放射治疗对肿瘤患者造血系统的影响及其相关发生机制的初步研究[D]. 苏州: 苏州大学, 2016.
Zuo ED. Preliminary study of impacts of radiation therapy on hematopoietic system in cancer patients and its relevant mechanisms[D]. Suzhou: Soochow University, 2016.[20] 北京医学奖励基金会肺癌青年专家委员会, 中国胸外科肺癌联盟. 肺癌骨转移诊疗专家共识(2019版)[J]. 中国肺癌杂志, 2019, 22(4): 187−207. DOI: 10.3779/j.issn.1009-3419.2019.04.01.
The Youth Specialists Committee of Lung Cancer, Beijing Medical Award Foundaton, Chinese Lung Cancer Union. Expert consensus on the diagnosis and treatment of bone metastasis in lung cancer (2019 version)[J]. Chin J Lung Cancer, 2019, 22(4): 187−207. DOI: 10.3779/j.issn.1009-3419.2019.04.01.[21] 中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2019年版)[J]. 中国癌症杂志, 2019, 29(8): 609−680. DOI: 10.19401/j.cnki.1007-3639.2019.08.009.
Chinese Anti-Cancer Association, Committee of Breast Cancer Society. Guidelines for the diagnosis and treatment of breast cancer of the Chinese Anti-Cancer Association (2019 version)[J]. China Oncol, 2019, 29(8): 609−680. DOI: 10.19401/j.cnki.1007-3639.2019.08.009.[22] 于林江. TE方案新辅助化疗在乳腺癌治疗中的应用效果及作用价值[J]. 数理医药学杂志, 2020, 33(2): 164−166. DOI: 10.3969/j.issn.1004-4337.2020.02.003.
Yu LJ. Application effect and value of TE regimen neoadjuvant chemotherapy in the treatment of breast cancer[J]. J Math Med, 2020, 33(2): 164−166. DOI: 10.3969/j.issn.1004-4337.2020.02.003.[23] 苏大伟. 吡柔比星为主的联合化疗方案治疗晚期乳腺癌的应用效果观察[J]. 现代诊断与治疗, 2018, 29(10): 1581−1582. DOI: 10.3969/j.issn.1001-8174.2018.10.039.
Su DW. Effect of pirorubicin-based combination chemotherapy in advanced breast cancer[J]. Mod Diagn Treat, 2018, 29(10): 1581−1582. DOI: 10.3969/j.issn.1001-8174.2018.10.039.[24] 罗恩茜, 倪青. 乳腺癌不同方案新辅助化疗后对粒细胞减少的影响及处理[J]. 重庆医学, 2018, 47(7): 971−974. DOI: 10.3969/j.issn.1671-8348.2018.07.030.
Luo EQ, Ni Q. Effect of neoadjuvant chemotherapy on granulocytopenia of breast cancer and its management[J]. Chongqing Med, 2018, 47(7): 971−974. DOI: 10.3969/j.issn.1671-8348.2018.07.030.[25] 石远凯, 孙燕, 于金明, 等. 中国晚期原发性肺癌诊治专家共识(2016年版)[J]. 中国肺癌杂志, 2016, 19(1): 1−15. DOI: 10.3779/j.issn.1009-3419.2016.01.01.
Shi YK, Sun Y, Yu JM, et al. China experts consensus on the diagnosis and treatment of advanced stage primary lung cancer (2016 version)[J]. Chin J Lung Cancer, 2016, 19(1): 1−15. DOI: 10.3779/j.issn.1009-3419.2016.01.01.[26] Hasegawa Y, Miura D, Kitamura C, et al. A randomized phase Ⅱ trial of gemcitabine plus carboplatin: biweekly versus standard schedules in patients with advanced non-small cell lung cancer[J]. Chemotherapy, 2013, 59(5): 346−353. DOI: 10.1159/000362222. [27] Clément-Zhao A, Auvray M, Aboudagga H, et al. Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer[J]. BJU Int, 2018, 121(2): 203−208. DOI: 10.1111/bju.13855. [28] Shimura Y, Suga Y, Itai S, et al. Comparison of tolerability between 2-weekly and 3-weekly Docetaxel regimen in castration-resistant prostate cancer[J]. Anticancer Res, 2020, 40(8): 4291−4297. DOI: 10.21873/anticanres.14431. [29] Yano R, Konno A, Watanabe K, et al. Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase Ⅱ and Ⅲ trials[J]. Int J Clin Oncol, 2013, 18(1): 96−104. DOI: 10.1007/s10147-011-0349-5. [30] 石远凯, 孙燕. 临床肿瘤内科手册[M]. 6版. 北京: 人民卫生出版社, 2015: 937.
Shi YK, Sun Y. Manual of medical oncology[M]. 6th ed. Beijing: People's Medical Publishing House, 2015: 937.[31] Papatheofanis FJ, Najib MM. Bone marrow recovery following use of systemic 153Sm-lexidronam and 89Sr-chloride for bone pain palliation after myelosuppressive therapy[J]. Int J Radiat Biol, 2009, 85(5): 448−453. DOI: 10.1080/09553000902818899. [32] Sciuto R, Festa A, Rea S, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial[J]. J Nucl Med, 2002, 43(1): 79−86. [33] Curtis KK, Adam TJ, Chen SC, et al. Anaemia following initiation of androgen deprivation therapy for metastatic prostate cancer: a retrospective chart review[J]. Aging Male, 2008, 11(4): 157−161. DOI: 10.1080/13685530802172438.
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