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Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma†
A randomized, double-blind, multicenter, comparative trial
Article first published online: 29 AUG 2003
Copyright © 2003 American Cancer Society
Volume 98, Issue 8, pages 1735–1744, 15 October 2003
How to Cite
Rosen, L. S., Gordon, D., Kaminski, M., Howell, A., Belch, A., Mackey, J., Apffelstaedt, J., Hussein, M. A., Coleman, R. E., Reitsma, D. J., Chen, B.-L. and Seaman, J. J. (2003), Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma. Cancer, 98: 1735–1744. doi: 10.1002/cncr.11701
Performed on behalf of the Zoledronic Acid Breast Cancer and Multiple Myeloma Study Group
Fax: (310) 998-3965
Dr. Hussein has received a research grant from Novartis
Dr. Coleman has received honoraria from Novartis
Dr. Seaman, Dr. Chen, and Dr. Reitsma are employed by Novartis Pharmaceuticals and may own stock in the company
- Issue published online: 3 OCT 2003
- Article first published online: 29 AUG 2003
- Manuscript Accepted: 14 JUL 2003
- Manuscript Revised: 23 JUN 2003
- Manuscript Received: 5 MAR 2003
- Novartis Pharmaceuticals Corporation (East Hanover, New Jersey)
- breast neoplasms;
- multiple myeloma;
- spinal cord compression
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. Cancer 2003. © 2003 American Cancer Society.