Cancer: pamidronate decreased skeletal complications in multiple myeloma.

Clinical bottom line (level 1b)

  1. Patients with advanced multiple myeloma who were given pamidronate were less likely to suffer a skeletal comlication (fracture, surgery to prevent fracture, spinal cord compression), than those given placebo (NNT = 8 at 29 months) .
  2. Patients who were given pamidronate had no clear difference in hypercalcaemia, than those given placebo.
Berenson et al: Journal of Clinical Oncology 1998; 16 (2): 593-602
Expires January 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 88 centres, US, Canada, Australia and New Zealand

392 patients (aged mean 64 years, 55% male) ambulatory adults with Durie-Salmon stage III multiple myeloma and at least one osteolytic lesion

Excluded if
  • skeletal-related event within two weeks before enrollment
  • serum creatinine >5.0 mg/dL
  • ascites
  • serum total bilirubin >2.5 mg/dL
  • abnormal ECG
  • treatment with bisphosphonate (except as part of the study) within 60 days before enrollment or at any time durin the study
  • treatment with a corticosteroid (unless part of chemotherapy regimen), calcitonin or mithramycin within two weeks before enrollment


    • Note:
  • Patients were stratified according to first-line regimen and second- or more line regimen.


    • Control Group: (n = 187, 179 analysed): placebo given as a 4 hour iv infusion every 4 weeks for 21 months
    Experimental Group: (n = 205, 198 analysed): pamidronate disodium 90 mg administered in 500 mL 5% dextrose in water, given as a 4 hour iv infusion at intervals of four weeks for 21 months

    100% followed for 29 months (median)
    Outcome notes:
    • skeletal events : pathologic fractures, spinal cord compression associated with vertebral compression fracture, surgery to treat or prevent pathologic fracture or spinal cord compression or radiation to bone.

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    skeletal events 29 months 91
    (50.84%)    		 76
    (38.38%)    		 24.0%
    (5.00% to 40.0%)    		 12.45%
    (2.48% to 22.43%)    		 8
    (4 to 40)
    hypercalcaemia 29 months 16
    (8.94%)    		 18
    (9.09%)    		 -2.00%
    (-93.0% to 46.0%)    		 -0.15%
    (-5.94% to 5.64%)    		 -656
    (NNT = 18 to infinity;
    NNH = 17 to infinity)

    Comments

    1. 78% of patients completed nine cycles of treatment and 41% completed 21 cycles.

    Citation

    1. Berenson JR, Lichtenstein A, Porter L, et al: Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Journal of Clinical Oncology 1998; 16 (2): 593-602
    Contributor: Clare Wotton and Musab Hayatli, January 2000
    Reviewer:

    Clinical Question.
    Patient advanced multiple myeloma
    Intervention or Exposure pamidronate
    Comparison placebo
    Outcome skeletal events