Gordon David H
US Oncology, San Antonio, TX 78217, USA.
Clin Breast Cancer. 2005 Jun;6(2):125-31. doi: 10.3816/CBC.2005.n.014.
Intravenous bisphosphonates are the preferred treatment to prevent skeletal complications for patients with breast cancer and bone metastases. Pamidronate, a single-nitrogen bisphosphonate, was the early standard of care for such patients based on 2 large, placebo-controlled trials involving 754 patients. Zoledronic acid, a new-generation bisphosphonate containing 2 nitrogens, was evaluated in 1130 patients with breast cancer in a large, randomized, comparative, phase III trial with pamidronate. At 25 months, zoledronic acid (4 mg) significantly reduced the overall risk of developing a skeletal-related event (SRE) by an additional 20% versus 90 mg pamidronate by multiple-event analysis. Furthermore, zoledronic acid was at least as effective as pamidronate in reducing the proportion of patients with > or = 1 SRE and in delaying the onset of SREs. Moreover, a retrospective subset analysis of 352 patients with > or = 1 osteolytic lesion proved zoledronic acid more effective than pamidronate in reducing the risk and delaying the onset of SREs. Intravenous ibandronate (6 mg via 1-2-hour infusion) was evaluated in a placebo-controlled, phase III trial of 466 patients and was significantly more effective than placebo in reducing the number of 12-week treatment periods in which an SRE occurred. The safety profiles among all intravenous bisphosphonates were similar; patients treated with intravenous bisphosphonates reported notably less bone pain but a higher incidence of mild to moderate transient infusion-related adverse events (eg, nausea, vomiting, myalgia, and anorexia) compared with placebo. In summary, intravenous bisphosphonates are effective for the treatment of bone metastases in patients with breast cancer and have similar safety profiles, but the shorter infusion time and greater efficacy of zoledronic acid in reducing overall skeletal morbidity provide advantages over other available agents.
静脉注射双膦酸盐是预防乳腺癌和骨转移患者骨骼并发症的首选治疗方法。帕米膦酸，一种单氮双膦酸盐，基于两项涉及754名患者的大型安慰剂对照试验，是此类患者的早期治疗标准。唑来膦酸，一种含两个氮的新一代双膦酸盐，在一项与帕米膦酸进行的大型、随机、对照、III期试验中，对1130名乳腺癌患者进行了评估。在25个月时，通过多事件分析，唑来膦酸（4毫克）与90毫克帕米膦酸相比，显著降低了发生骨相关事件（SRE）的总体风险，额外降低了20%。此外，唑来膦酸在降低≥1次SRE患者比例和延迟SRE发作方面至少与帕米膦酸一样有效。此外，对352名≥1处溶骨性病变患者的回顾性子集分析证明，唑来膦酸在降低SRE风险和延迟其发作方面比帕米膦酸更有效。静脉注射伊班膦酸（通过1 - 2小时输注给予6毫克）在一项466名患者的安慰剂对照III期试验中进行了评估，在减少发生SRE的12周治疗周期数量方面显著优于安慰剂。所有静脉注射双膦酸盐的安全性概况相似；与安慰剂相比，接受静脉注射双膦酸盐治疗的患者报告的骨痛明显较少，但轻度至中度短暂输注相关不良事件（如恶心、呕吐、肌痛和厌食）的发生率较高。总之，静脉注射双膦酸盐对乳腺癌患者的骨转移有效且安全性概况相似，但唑来膦酸输注时间较短且在降低总体骨骼发病率方面疗效更佳，比其他可用药物具有优势。
