唑来膦酸两种剂量频次在乳腺癌骨转移治疗中的对比研究
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摘要
目的对比研究唑来膦酸两种剂量频次(4周和12周)在治疗乳腺癌骨转移中的临床应用,旨在为乳腺癌骨转移患者应用唑来膦酸提供参考。方法取2012年9月～2016年9月我院接诊的乳腺癌患者82例,按不同剂量及给药频次分为4周组(n=42)和12周组(n=40)两组,均接受唑来膦酸治疗,通过检测患者血清β-CTX和PICP水平,评价治疗疗效,并同时观察、对比骨相关事件(包括骨折、疼痛、脊髓压迫、高血钙症及需手术治疗或放射治疗的骨并发症等)及毒副反应(包括肝肾毒性、胃肠道反应、下颌骨坏死等)的发生率。结果研究两组基线特征有可比性。两种治疗方式的不良事件发生率无明显差异、毒副反应发生率无明显差异(P>0.05),治疗前后血清β-CTX和PICP水平均明显降低(P<0.05)。结论唑来膦酸两种剂量频次对乳腺癌骨转移的疗效、毒副反应概率无明显差异,临床可根据乳腺癌骨转移患者病情选择使用。
Objective To compare the clinical application of two doses of zoledronic acid(4 weeks and 12 weeks) in the treatment of bone metastasis of breast cancer, aiming to provide reference for the application of zoledronic acid in patients with breast cancer. Methods A total of 82 patients with breast cancer who were admitted in our hospital from September 2012 to September 2016 were divided into 4 weeks group(n=42) and 12 weeks group(n=40) according to different doses and frequency of administration. The two groups received zoledronic acid. The therapeutic effect was evaluated by measuring the serum levels of β-CTX and PICP. At the same time, the incidences of bone-related events(including fractures, pain, spinal cord compression, hypercalcemia, and bone complications requiring surgery or radiation therapy) and toxic side effects(including liver and kidney toxicity, gastrointestinal reactions, mandibular necrosis, etc.)were observed and compared. Results The baseline characteristics of the two groups were comparable. There was no significant difference in the probability of adverse events and side effects between the two treatments(P>0.05). Serumβ-CTX and PICP levels were significantly reduced after treatment(P<0.05). Conclusion There was no significant difference in the efficacy on breast cancer bone metastasis and toxic side reaction probability between the two doses of zoledronic acid. It can be selected according to the condition of breast cancer patients with bone metastases.
Objective To compare the clinical application of two doses of zoledronic acid(4 weeks and 12 weeks) in the treatment of bone metastasis of breast cancer, aiming to provide reference for the application of zoledronic acid in patients with breast cancer. Methods A total of 82 patients with breast cancer who were admitted in our hospital from September 2012 to September 2016 were divided into 4 weeks group(n=42) and 12 weeks group(n=40) according to different doses and frequency of administration. The two groups received zoledronic acid. The therapeutic effect was evaluated by measuring the serum levels of β-CTX and PICP. At the same time, the incidences of bone-related events(including fractures, pain, spinal cord compression, hypercalcemia, and bone complications requiring surgery or radiation therapy) and toxic side effects(including liver and kidney toxicity, gastrointestinal reactions, mandibular necrosis, etc.)were observed and compared. Results The baseline characteristics of the two groups were comparable. There was no significant difference in the probability of adverse events and side effects between the two treatments(P>0.05). Serumβ-CTX and PICP levels were significantly reduced after treatment(P<0.05). Conclusion There was no significant difference in the efficacy on breast cancer bone metastasis and toxic side reaction probability between the two doses of zoledronic acid. It can be selected according to the condition of breast cancer patients with bone metastases.
引文
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[14]Cheng Meng,Cui Yanzhi,Li Ying,et al.Clinical application and mechanism of zoledronic acid in adjuvant therapy of breast cancer[J].Chinese Journal of Cancer,2014,23(5):394-398.
[15]Mathew A,Brufsky A.Bisphosphonates in breast cancer[J].Int J Cancer,2015,137(4):753-764.
[16]Santini D,Stumbo L,Spoto C,et al.Bisphosphonates as anticancer agents in early breast cancer:Pre clinical and clinical evidence[J].Breast Cancer Res,2015,17(1):121.
[17]Nienhuis HH,Arjaans M,Timmer-Bosscha H,et al.Human stromal cells are required for an anti-breast cancer effect of zole-dronic acid[J].Oncotarget,2015,6(27):24436-24447.
[18]Alcaraz A,Gonzalez-Lopez R,Morote J,et al.Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid:The TUGAMO study[J].British Journal of Cancer,2013,109(1):121-130.
[19]Lumachi F,Santeufemia DA,Conte AD,et al.Carboxyterminal telopeptide(CTX)and amino-terminal propeptide(PINP)of type I collagen as markers of bone metastases in patients with non-small cell lung cancer[J].Anticancer Res,2013,33(6):2593-2596.
[20]Amadori D,Aglietta M,Alessi B,et al.Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer(ZOOM):a phase 3,open-label,randomised,non-inferiority trial[J].Lancet Oncol,2013,14(7):663-670.
[21]Hortobagyi GN,Van Poznak C,Harker WG,et al.Continued Treatment Effect of Zoledronic Acid Dosing Every12 vs 4 Weeks in Women With Breast Cancer Metastatic to Bone:The OPTIMIZE-2 Randomized Clinical Trial[J].JAMA Oncology,2017,3(7):906-912.
[2]Nadia Rucci,Patrizia Sanità,Simona Delle Monache,et al.Molecular pathogenesis of bone metastases in breast cancer:Proven and emerging therapeutic targets[J].World Journal of Clinical Oncology,2014,5(3):335-347.
[3]Addison CL,Pond GR,Zhao H,et al.Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases[J].Springerplus,2014,3(1):577.
[4]Kenessey István,Kói Krisztina,Horváth Orsolya,et al.KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models[J].Oncotarget,2016,7(48):79503-79514.
[5]Khalafallah AA,Slancar M,Cosolo W,et al.Long-term safety of monthly zoledronic acid therapy beyond 1 year in patients with advanced cancer involving bone(Lo T-ESS):A multicentre prospective phase 4 study[J].European Journal of Cancer Care,2018,27(2):e12638.
[6]Himelstein AL,Rui Q,Novotny PJ,et al.CALGB 70604(Alliance):A randomized phaseⅢstudy of standard dosing vs longer interval dosing of zoledronic acid in metastatic cancer[J].J Clin Oncol,2015,33(33):151-158.
[7]Xu Xin.Clinical study of zoledronic acid for bone metastasis in breast cancer[J].Chinese Modern Docto,2014,52(13):151-153,156.
[8]Gunaldi M,Afsar CU,Duman BB,et al.Effect of the cumulativedose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws[J].Oncol Lett,2015,10(1):439-442.
[9]Barrantes-Gonzalez M,Espona-Quer M,Salas E,et al.Bisphos-phonate-induced cutaneous adverse events:The difficulty of asses-sing imputability through patch testing[J].Dermatology,2014,229(3):163-168.
[10]Lüftner D,Niepel D.Breast cancer and bone metastases:A call for appropriate treatment[J].Supportive Care in Cancer:Official Journal of the Multinational Association of Supportive Care in Cancer,2016,24(10):4075-4077.
[11]Singh T,Kaur V,Kumar M,et al.The critical role of bisphospho-nates to target bone cancer metastasis An overview[J].J Drug Tar-geting,2015,23(1):1-15.
[12]Hilton JF,Clemons M,Pond G,et al.Effects on bone resorption markers of continuing pamidronate or switching to zoledronic acid in patients with high risk bone metastases from breast cancer[J].Journal of Bone Oncology,2018,10:6-13.
[13]Caroline Wilson,Samantha Hinsley,Helen Marshall,et al.Reproductive hormone analyses and effects of adjuvant zoledronic acid in early breast cancer-An AZURE(BIG01/04)sub-study[J].Journal of Bone Oncology,2017,9:48-54.
[14]Cheng Meng,Cui Yanzhi,Li Ying,et al.Clinical application and mechanism of zoledronic acid in adjuvant therapy of breast cancer[J].Chinese Journal of Cancer,2014,23(5):394-398.
[15]Mathew A,Brufsky A.Bisphosphonates in breast cancer[J].Int J Cancer,2015,137(4):753-764.
[16]Santini D,Stumbo L,Spoto C,et al.Bisphosphonates as anticancer agents in early breast cancer:Pre clinical and clinical evidence[J].Breast Cancer Res,2015,17(1):121.
[17]Nienhuis HH,Arjaans M,Timmer-Bosscha H,et al.Human stromal cells are required for an anti-breast cancer effect of zole-dronic acid[J].Oncotarget,2015,6(27):24436-24447.
[18]Alcaraz A,Gonzalez-Lopez R,Morote J,et al.Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid:The TUGAMO study[J].British Journal of Cancer,2013,109(1):121-130.
[19]Lumachi F,Santeufemia DA,Conte AD,et al.Carboxyterminal telopeptide(CTX)and amino-terminal propeptide(PINP)of type I collagen as markers of bone metastases in patients with non-small cell lung cancer[J].Anticancer Res,2013,33(6):2593-2596.
[20]Amadori D,Aglietta M,Alessi B,et al.Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer(ZOOM):a phase 3,open-label,randomised,non-inferiority trial[J].Lancet Oncol,2013,14(7):663-670.
[21]Hortobagyi GN,Van Poznak C,Harker WG,et al.Continued Treatment Effect of Zoledronic Acid Dosing Every12 vs 4 Weeks in Women With Breast Cancer Metastatic to Bone:The OPTIMIZE-2 Randomized Clinical Trial[J].JAMA Oncology,2017,3(7):906-912.