Hypercalcaemia: regular pamidronate reduced skeletal complications in metastatic breast cancer

Clinical bottom line (level 1b)

  1. Women with breast cancer and bony metastases who had regular pamidronate were less likely to suffer skeletal complications (NNT = 8 at 12 months)
  2. In these patients, pathological fractures were not clearly reduced overall
  3. In these patients
    • fewer required radiation to bone (NNT = 7 at 12 months)
    • fewer required surgery (NNT = 17 at 12 months) , and
    • fewer developed hypercalcaemia (NNT = 16 at 12 months)
Hortobagyi et al: New England Journal of Medicine 1996; 335: 1785-1791
Expires March 2003

The study

Single-blinded ?concealed randomised trial with intention-to-treat
Setting: 97 hospitals, North America, Australia and New Zealand

382 patients (aged Mean age 57 +- 12, 100% female) Breast cancer, receiving chemotherapy and with at least one predominantly lytic metastatic bone lesion >= 1 cm in diameter

Excluded if
  • Skeletal complication: pathological fracture, need for radiation to bone or bone surgery, spinal cord compression
  • Serum calcium > 3.0 mmol/l during 2 weeks before enrolment
  • Serum creatinine > 220 mmol/dl
  • New York Heart Association rand class III or IV
  • On bisphosphate during last 60 days
  • Treated for bone pain with radiation, steroids, calcitonin or plicamycin within last 3 months


    • Note:
  • Patients were stratified on performance status before randomisation


    • Control Group: (n = 197, 197 analysed): Placebo
    Experimental Group: (n = 185, 185 analysed): Pamidronate 90 mg iv. over 2 hours monthly for 12 months
    48% completed all 12 cycles
    100% followed for 12 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    Any skeletal complication 12 months 110
    (558%)    		 79
    (42.7%)    		 24%
    (6% to 38%)    		 13.13%
    (3.19% to 23.1%)    		 8
    (4 to 31)
    any pathological fracture 12 months 96
    (48.7%)    		 79
    (42.7%)    		 12%
    (-9% to 30%)    		 6.0%
    (-3.95% to 16.0%)    		 17
    (NNT = 6 to infinity;
    NNH = 25 to infinity)
    pathologic fracture, non-vertebral 12 months 59
    (30.0%)    		 37
    (20.0%)    		 33%
    (4% to 53%)    		 10.0%
    (1.34% to 18.6%)    		 10
    (5 to 75)
    pathologic fracture, vertebral 12 months 37
    (18.8%)    		 42
    (22.7%)    		 -21%
    (-79% to 18%)    		 -3.92%
    (-12.1% to 4.21%)    		 -26
    (NNT = 24 to infinity;
    NNH = 8 to infinity)
    radiation to bone 12 months 65
    (33.0%)    		 36
    (19.5%)    		 41%
    (16% to 59%)    		 13.5%
    (4.84% to 22.2%)    		 7
    (4 to 21)
    surgery on bone 12 months 19
    (9.64%)    		 7
    (3.78%)    		 61%
    (9% to 83%)    		 5.86%
    (0.91% to 10.8%)    		 17
    (9 to 110)
    hypercalcaemia 12 months 24
    (12.2%)    		 11
    (7.57%)    		 51%
    (3% to 75%)    		 6.24%
    (0.54% to 11.9%)    		 16
    (8 to 186)

  • These benefits were found to extend out to 2 years.

    • Comments

    1. Bisphosphonates are now an integral part of the management of patients with metastatic disease.

    Citation

    1. Hortobagyi GN, Theriault RL, Porter L, et al: Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. New England Journal of Medicine 1996; 335: 1785-1791
    Contributor: Chris Ball and Musab Hayatli, October 2000
    Reviewer: Michael Dixon

    Clinical Question.
    Patient breast cancer and metastases
    Intervention or Exposure pamidronate
    Outcome pain, hypercalcaemia, fractures