Green Jonathan R
Novartis Institutes for BioMedical Research, Basel, Switzerland.
Acta Oncol. 2005;44(3):282-92. doi: 10.1080/02841860510029644.
Patients with prostate cancer are at risk for skeletal complications resulting from treatment-induced bone loss and for bone metastases. The therapeutic potential of zoledronic acid for the treatment of prostate cancer has been demonstrated in both preclinical and clinical studies. In patients receiving androgen-deprivation therapy, zoledronic acid increases bone mineral density, and, in patients with bone metastases, it reduces the incidence of skeletal complications. Preclinical studies have also demonstrated the antitumor potential of bisphosphonates. Specifically, zoledronic acid inhibits proliferation and induces apoptosis of human prostate cancer cell lines in vitro and has enhanced antitumor activity when combined with taxanes. Animal models have further shown that bisphosphonates decrease tumor-induced osteolysis and reduce skeletal tumor burden. In a model of prostate cancer, zoledronic acid significantly inhibited growth of both osteolytic and osteoblastic tumors and reduced circulating levels of prostate-specific antigen. These studies suggest that zoledronic acid has the potential to inhibit bone metastasis and bone lesion progression in patients with prostate cancer.
前列腺癌患者存在因治疗引起的骨质流失导致骨骼并发症以及发生骨转移的风险。唑来膦酸治疗前列腺癌的治疗潜力已在临床前和临床研究中得到证实。在接受雄激素剥夺治疗的患者中，唑来膦酸可增加骨矿物质密度，而在有骨转移的患者中，它可降低骨骼并发症的发生率。临床前研究也已证明双膦酸盐的抗肿瘤潜力。具体而言，唑来膦酸在体外可抑制人前列腺癌细胞系的增殖并诱导其凋亡，与紫杉烷联合使用时具有增强的抗肿瘤活性。动物模型进一步表明，双膦酸盐可减少肿瘤诱导的骨溶解并减轻骨骼肿瘤负担。在前列腺癌模型中，唑来膦酸显著抑制溶骨性和成骨性肿瘤的生长，并降低前列腺特异性抗原的循环水平。这些研究表明，唑来膦酸有可能抑制前列腺癌患者的骨转移和骨病变进展。
