The bisphosphonates that have been studied include pamidronate, etidronate, and clodronate. All three may be very effective in controlling hypercalcemia of malignancy. A randomized comparison of the three bisphosphonates demonstrated the superiority of pamidronate in both rate and duration of response. The toxic effects of the bisphosphonates include transient fever, local reactions at the infusion site, hypomagnesemia, hypophosphatemia, and occasional flulike syndrome. Other agents used in the second-line treatment of hypercalcemia of malignancy include plicamycin, calcitonin, gallium nitrate, and the glucocorticoids.
Immobilization leads to a rapid increase in bone resorption.
Mobilization therefore is an important but frequently neglected component in the treatment of hypercalcemia of malignancy. Therefore, efforts to decrease intestinal absorption of calcium by dietary restriction are of limited therapeutic value. The syndrome usually occurs within six to 72 hours after the initiation of therapy and is characterized by hyperkalemia, hyperuricemia, and hyperphosphatemia with secondary hypocalcemia. Tumor lysis syndrome is most often seen in patients with lymphoma or leukemia but also in patients with a variety of solid tumors. A large tumor burden, a high growth fraction, an increased pretreatment lactate dehydrogenase level, an increased pretreatment uric acid level, or preexisting renal insufficiency increases the risk of tumor lysis syndrome.