Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group

J Clin Oncol. 1998 Jun;16(6):2038-44. doi: 10.1200/JCO.1998.16.6.2038.

Abstract

Purpose: Pamidronate, an aminobisphosphonate, has been shown to lower the risk of skeletal complications associated with lytic bone lesions for up to 1 year in women with stage IV breast cancer who received chemotherapy. We studied the long-term effectiveness and safety of continued treatment with intravenous pamidronate infusions for up to 2 years.

Patients and methods: Three hundred eighty-two women with metastatic breast cancer and lytic bone lesions who received chemotherapy were randomly assigned to receive either 90 mg of pamidronate or placebo intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel-group trial. Patients were evaluated monthly for 2 years for skeletal complications, which included pathologic fractures, need for radiation or surgery to treat bone complications, spinal cord compression, and hypercalcemia. Bone pain, analgesic use, bone biochemical markers, performance status, quality of life, radiologic response in bone, and survival were also evaluated.

Results: As in the first year of treatment, the proportion of patients with any skeletal complication was significantly less for the pamidronate than the placebo group at 15, 18, 21, and 24 months (P < .001). The proportions of patients with any pathologic fracture (i.e., vertebral and nonvertebral fractures), need for radiation or surgery to treat bone complications, and hypercalcemia were also statistically less for the pamidronate than the placebo group. The median time to the first skeletal complication was 13.9 months in the pamidronate-treated women and 7.0 months in the placebo group (P < .001). Long-term treatment did not result in any unexpected adverse events. Survival did not differ between the two groups.

Conclusion: The risk for osteolytic bone lesion complications in metastatic breast cancer was significantly decreased with monthly infusions of 90 mg of pamidronate, and this effect was maintained for at least 2 years. Pamidronate is a useful adjunct to standard chemotherapy in the palliative treatment of metastatic breast cancer.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / blood
  • Analgesics / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / complications*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Calcium / urine
  • Creatinine / urine
  • Diphosphonates / administration & dosage*
  • Diphosphonates / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxyproline / urine
  • Osteolysis / blood
  • Osteolysis / complications
  • Osteolysis / prevention & control*
  • Osteolysis / urine
  • Pain / drug therapy
  • Pain / epidemiology
  • Pamidronate
  • Survival Rate
  • Treatment Outcome

Substances

  • Analgesics
  • Diphosphonates
  • Creatinine
  • Alkaline Phosphatase
  • Pamidronate
  • Hydroxyproline
  • Calcium