Academic Unit of Clinical Oncology, Broomcross Building, Weston Park Hospital, Sheffield S10 2SJ, UK.
J Natl Cancer Inst. 2012 Jul 18;104(14):1059-67. doi: 10.1093/jnci/djs263. Epub 2012 Jul 2.
Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.
双膦酸盐和地舒单抗等骨靶向治疗药物可减少骨质吸收，已知可降低骨骼并发症风险，并预防恶性骨病患者的治疗相关骨质流失。此外，这些药物可能通过抑制肿瘤和骨髓微环境中骨细胞之间生长因子和细胞因子信号的“恶性循环”，从而改变骨破坏的进程。药物对干细胞龛的影响、对癌细胞的直接作用以及免疫调节也可能有一定的贡献。在早期（I、II 和 III 期）乳腺癌中，用双膦酸盐唑来膦酸治疗可改善无病生存和总生存。在诊断时已绝经的女性和接受抑制卵巢功能的促性腺激素释放激素类似物戈舍瑞林治疗的绝经前内分泌敏感型疾病的女性中，生存改善尤为显著，因为该药物可通过抑制卵巢激素的产生来抑制卵巢功能。此外，在去势抵抗性前列腺癌中，用地舒单抗治疗可延缓骨转移的发生。这些结果强烈支持辅助使用骨靶向治疗，但提示生殖激素是一个重要的治疗修饰因素，需要加以考虑。在晚期（IV 期，即转移性）癌症中，接受唑来膦酸治疗的多发性骨髓瘤患者和骨质破坏迅速的其他实体瘤患者观察到了生存获益。在此，我们批判性地回顾了越来越多的证据，以支持骨靶向治疗具有疾病修饰作用，并讨论了其对临床管理的影响。
