[Medical treatment of malignant hypercalcemia]

Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.