Hypercalcaemia: APD, mithramycin and corticosteroids/calcitonin decreased serum calcium.

Clinical bottom line (level 1b-)

  1. In patients with malignant hypercalcaemia, aminohydroxypropylidene diphosphate (APD), mithramycin and corticosteroids/calcitonin all decreased serum calcium effectively.
  2. Corticosteroids/calcitonin decreased serum calcium more quickly than mithramycin or APD, but at 9 days serum calcium levels with APD were significantly lower than with the others.
Ralston et al: Lancet 1985; 2 (8461): 907-910
Expires June 2003

The study

?blinded concealed randomised trial without intention-to-treat
Setting: general hospital, UK

39 patients (aged ?, ?% male) cancer-associated hypercalcaemia (adjusted serum calcium >2.8 mmol/l)
Control Group: (n = 13, 13 analysed): prednisolone 40 mg/day orally in divided doses plus salmon calcitonin 400 IU every 8 hours subcutaneously continued for 9 days
Experimental Group: (n = 13, 13 analysed): aminohydroxypropylidene diphosphate (APD) 15 mg in 250 ml saline daily until serum calcium was normal
Experimental Group: (n = 13, 13 analysed): mithramycin 25 µ g/kg in 500 ml dextrose and repeated after two days if serum calcium remained above 2.9 mmol/l
All patients were rehydrated with iv saline 500 ml every 4 hours for a minimum of 48 hours, then 500 ml every 6 hours for 12 hours before antihypercalcaemic treatment was given, and then given 2 l/day until serum calcium had fallen.
100% followed for 9 days

The evidence

  • Time taken for serum calcium to fall a median of 0.35 mmol/l took:
    • 24 hours in the corticosteroid/calcitonin group
    • 48 hours in the mithramycin group
    • 72 hours in the APD group
  • Serum calcium levels were significantly lower in APD treated than in corticosteroid/calcitonin treated patients at both 6 and 9 days, and mithramycin treated patients at 9 days.

    • Citation

    1. Ralston SH, Gardner MD, Dryburgh FJ, et al: Comparison of aminohydroxypropylidene diphosphate, mithramycin, and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia. Lancet 1985; 2 (8461): 907-910
    Contributor: Clare Wotton and Musab Hayatli, June 2000
    Reviewer:

    Clinical Question.
    Patient malignant hypercalcaemiahypercalcemia
    Intervention or Exposure aminohydroxypropylidende diphosphate or mithramycin
    Comparison corticosteroids and calcitonin
    Outcome calcium lowering