Cancer-related hypercalcemia is a major problem in clinical oncology. We recently showed that gallium nitrate directly inhibits in vitro bone resorption despite stimulation with parathyroid hormone and osteoclast activating factor. In a pilot study, we further demonstrated that this drug is effective treatment for cancer-related hypercalcemia. This application seeks to continue this area of clinical investigation. We plan to conduct two clinical studies: 1. Four dose-schedules of drug administration will establish a minimal effective dose for use in cancer-related hypercalcemia. Pharmacokinetics of gallium nitrate will also be studied in this trial to correlate hypocalcemic response with plasma drug concentrations. 2. When an optimal dose is established in the preceding study, we will conduct a prospective, randomized comparison of gallium nitrate vs. best standard treatment for patients with resistant cancer-related hypercalcemia. Our preliminary investigations have identified gallium nitrate as a compound with major effects upon calcium homeostasis. In this application, we expect to demonstrate that gallium nitrate is at least as effective as the best conventional treatment for cancer-related hypercalcemia and that it causes less toxicity. The results of these studies should significantly further the development of gallium nitrate for treatment of this indication.