Update on the medical treatment of hypercalcemia of malignancy.

Recent information on the pathophysiology and treatment of hypercalcemia of malignancy is reviewed, and the roles of two new agents, gallium nitrate and pamidronate, are discussed. Current evidence suggests that parathyroid hormone-related protein is the most important mediator of humoral hypercalcemia of malignancy. In patients with local osteolytic hypercalcemia, cytokines have been implicated as mediators. Effective treatment of hypercalcemia of malignancy may improve patients' quality of life, although an episode of hypercalcemia is a poor prognostic indicator for survival. Gallium nitrate is more effective than salmon calcitonin and possibly more effective than etidronate in the treatment of hypercalcemia of malignancy. The primary adverse effect of gallium nitrate is nephrotoxicity, and its use must be avoided in patients who have renal dysfunction or who are receiving nephrotoxic drugs. Pamidronate is more effective than etidronate in the treatment of hypercalcemia of malignancy and can be administered as a single i.v. dose. The adverse effects of pamidronate include mild fever, hypocalcemia, and hypophosphatemia. Compared with gallium nitrate, pamidronate offers a more convenient dosing regimen, is less frequently associated with nephrotoxicity, and is less expensive. Single i.v. doses of either pamidronate or plicamycin effectively lower serum calcium levels and are reasonable choices for maintenance therapy. Gallium nitrate and pamidronate may be slightly more effective than previously available agents for initial treatment of hypercalcemia. Pamidronate currently offers the best combination of effectiveness, ease of administration, and a low rate of adverse effects.