Hypercalcaemia and cancer: pamidronate was more effective than placebo at achieving normocalcaemia.

Clinical bottom line (level 1b)

  1. Patients with cancer and hypercalcaemia who took pamidronate compared with placebo were more likely to become normocalcaemic (NNT = 2 at 7 days) , and are slower to revert (NNT = 3 at 7 days) .
  2. More developed a fever (NNH = 5 at 7 days) .
Gucalp et al: Archives of Internal Medicine 1994; 154: 1935-1944
Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: twelve university hospitals, USA

69 patients (aged mean 55 years, 55% female) with histologically-proven malignant neoplasm and a calcium 3.0 mmol/l or more after adequate rehydration ( three litres of 0.9% saline iv and a urine output of two or more litres over 24 hours)

Excluded if
  • Cr > 440 micromol/l
  • potassium <3.5
  • congestive heart failure
  • other cause of hypercalcaemia
  • previous therapy with pamidronate
  • <18 years old


    • Control Group: (n = 23, 23 analysed): placebo
    Experimental Group: (n = 46, 46 analysed): pamidronate 60 mg in 1000 ml 0.9% saline over 24 hours (23 patients) or in 500 ml 0.9% saline over 4 hours (23 patients)
    Patients continued two litres of 0.9% saline with two litres of urine output per day. Patients received no other cancer therapy during study, and had furosemide only if they were overloaded.
    100% followed for 60 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    still hypercalcaemic 7 days 18
    (78.3%)    		 14
    (30.4%)    		 61%
    (37% to 76%)    		 47.8%
    (26.4% to 69.3%)    		 2
    (1 to 4)
    fever due to medication 7 days 0
    (0.00%)    		 10
    (21.7%)    		 %
    (% to %)    		 -21.7%
    (-33.7% to -9.82%)    		 -5
    (-10 to -3)
    relapse 7 days 21
    (91.3%)    		 24
    (52.2%)    		 43%
    (23% to 58%)    		 39.1%
    (20.7% to 57.6%)    		 3
    (2 to 5)

  • No significant difference between two pamidronate regimens (4 hourly: 18/23 normocalcaemic; 24 hourly: 14/23 normocalcaemic) NNT = 6 (95% CI: NNT = 2 to inf; NNH = 11 to inf).
  • No significant difference in length of time to achieve normocalcaemia (~ 6 days; range 1 to 59) or time normocalcaemic (~8 days: range 1 to 60).

    • Citation

    1. Gucalp R, Theriault R, Gill I, et al: treatment of cancer-associated hypercalcaemia: double-blinded comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone. Archives of Internal Medicine 1994; 154: 1935-1944
    Search Terms: hypercalc* in Cochrane
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient cancer and hypercalcaemia
    Intervention or Exposure pamidronate
    Comparison placebo
    Outcome normocalcaemia, side-effects