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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

  1. Lee S. Rosen M.D.1,‡,*,
  2. David Gordon M.D.2,
  3. Mary Kaminski M.D.3,
  4. Anthony Howell B.Sc., M.Sc., M.B., B.S.4,
  5. Andrew Belch M.D.5,
  6. John Mackey M.D.5,
  7. Justus Apffelstaedt M.D.6,
  8. Mohamad A. Hussein M.D.7,§,
  9. Robert E. Coleman M.D.8,¶,
  10. Dirk J. Reitsma M.D.9,‖,
  11. Bee-Lian Chen Ph.D.9,‖,
  12. John J. Seaman Pharm.D.9,‖

Article first published online: 29 AUG 2003

DOI: 10.1002/cncr.11701

Issue

Cancer

Cancer

Volume 98, Issue 8, pages 1735–1744, 15 October 2003

Additional Information

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

Author Information

  1. 1

    Developmental Therapeutics, Cancer Institute Medical Group, Santa Monica, California

  2. 2

    Medical Oncology/Hematology, US Oncology, San Antonio, Texas

  3. 3

    American Medical Research Institute, Kennesaw, Georgia

  4. 4

    CRC Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester, United Kingdom

  5. 5

    Department of Medicine, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada

  6. 6

    Mamma Clinic, Tygerberg Hospital, Cape Town, South Africa

  7. 7

    Myeloma Research Program, Cleveland Clinic, Cleveland, Ohio

  8. 8

    Academic Unit of Oncology, Weston Park Hospital, Cancer Research Centre, Sheffield, United Kingdom

  9. 9

    Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

  1. ‡

    Fax: (310) 998-3965

  2. §

    Dr. Hussein has received a research grant from Novartis

  3. Dr. Coleman has received honoraria from Novartis

  4. ‖

    Dr. Seaman, Dr. Chen, and Dr. Reitsma are employed by Novartis Pharmaceuticals and may own stock in the company

*Director of Developmental Therapeutics, Cancer Institute Medical Group, 2001 Santa Monica Boulevard, Suite 560W, Santa Monica, CA 90095

  1. †

    Performed on behalf of the Zoledronic Acid Breast Cancer and Multiple Myeloma Study Group

Publication History

  1. Issue published online: 3 OCT 2003
  2. Article first published online: 29 AUG 2003
  3. Manuscript Accepted: 14 JUL 2003
  4. Manuscript Revised: 23 JUN 2003
  5. Manuscript Received: 5 MAR 2003

Funded by

  • Novartis Pharmaceuticals Corporation (East Hanover, New Jersey)

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Keywords:

  • breast neoplasms;
  • fractures;
  • spontaneous;
  • hypercalcemia;
  • multiple myeloma;
  • osteolysis;
  • spinal cord compression

Zoledronic acid (4 mg) administered as a 15-minute intravenous infusion every 3–4 weeks is safe and well tolerated in patients with bone lesions secondary to breast carcinoma or multiple myeloma. During this 25-month study, it was found that zoledronic acid was more effective, based on multiple-event analysis, than pamidronate in reducing the risk of developing skeletal complications in patients with bone lesions from metastatic breast carcinoma and multiple myeloma.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI 10.1002/cncr.11701

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