Rosen Lee S, Gordon David, Kaminski Mary, Howell Anthony, Belch Andrew, Mackey John, Apffelstaedt Justus, Hussein Mohamad A, Coleman Robert E, Reitsma Dirk J, Chen Bee-Lian, Seaman John J
Developmental Therapeutics, Cancer Institute Medical Group, Santa Monica, California 90095, USA.
Cancer. 2003 Oct 15;98(8):1735-44. doi: 10.1002/cncr.11701.
The goal of the current study was to compare the long-term (25-month) safety and efficacy of zoledronic acid with pamidronate in patients with bone lesions secondary to advanced breast carcinoma or multiple myeloma.
Patients (n = 1648) were randomized to receive 4 mg or 8 mg (reduced to 4 mg) zoledronic acid as a 15-minute infusion or to receive 90 mg pamidronate as a 2-hour infusion every 3-4 weeks for 24 months. The primary endpoint was the proportion of patients with at least 1 skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate, and multiple-event analysis. Hypercalcemia of malignancy (HCM) was included as an SRE in some secondary analyses.
After 25 months of follow-up, zoledronic acid reduced the overall proportion of patients with an SRE and reduced the skeletal morbidity rate similar to pamidronate. Compared with pamidronate, zoledronic acid (4 mg) reduced the overall risk of developing skeletal complications (including HCM) by an additional 16% (P = 0.030). In patients with breast carcinoma, zoledronic acid (4 mg) was significantly more effective than pamidronate, reducing the risk of SREs by an additional 20% (P = 0.025) compared with pamidronate and by an additional 30% in patients receiving hormonal therapy (P = 0.009). Zoledronic acid (4 mg) and pamidronate were tolerated equally well. The most common adverse events included bone pain, nausea, and fatigue.
Long-term follow-up data confirm that zoledronic acid was more effective than pamidronate in reducing the risk of skeletal complications in patients with bone metastases from breast carcinoma and was of similar efficacy in patients with multiple myeloma.
本研究的目的是比较唑来膦酸与帕米膦酸对晚期乳腺癌或多发性骨髓瘤继发骨病变患者的长期（25个月）安全性和疗效。
1648例患者被随机分组，每3 - 4周接受一次15分钟静脉输注4mg或8mg（后减至4mg）唑来膦酸，或接受一次2小时静脉输注90mg帕米膦酸，共24个月。主要终点是至少发生1次骨相关事件（SRE）的患者比例，SRE定义为病理性骨折、脊髓压迫、放射治疗或骨手术。次要分析包括首次SRE发生时间、骨发病率和多事件分析。在一些次要分析中，恶性肿瘤高钙血症（HCM）被纳入SRE。
经过25个月的随访，唑来膦酸降低了发生SRE的患者总体比例，并降低了骨发病率，与帕米膦酸相似。与帕米膦酸相比，唑来膦酸（4mg）将发生骨并发症（包括HCM）的总体风险又降低了16%（P = 0.030）。在乳腺癌患者中，唑来膦酸（4mg）比帕米膦酸显著更有效，与帕米膦酸相比，将SRE风险又降低了20%（P = 0.025），在接受激素治疗的患者中降低了30%（P = 0.009）。唑来膦酸（4mg）和帕米膦酸的耐受性相当。最常见的不良事件包括骨痛、恶心和疲劳。
长期随访数据证实，唑来膦酸在降低乳腺癌骨转移患者骨并发症风险方面比帕米膦酸更有效，在多发性骨髓瘤患者中疗效相似。
