Treating cancer-related hypercalcemia with gallium nitrate

Gallium nitrate is an approved therapy for symptomatic, cancer-related hypercalcemia unresponsive to adequate hydration, the most common life-threatening metabolic disorder of cancer. Initially developed because of its antineoplastic properties, gallium nitrate demonstrated the ability to reduce serum calcium levels in early trials. Although the mechanism by which gallium nitrate corrects hypercalcemia is not fully understood, it appears to involve multiple effects (inhibition of osteoclast-mediated bone resorption, stimulation of bone formation, and alteration of the mineral composition and properties of bone); however, gallium nitrate is not cytotoxic to bone cells. In randomized trials for moderate-to-severe cancer-related hypercalcemia, gallium nitrate was well tolerated and produced a higher rate and longer duration of normocalcemia relative to calcitonin and the bisphosphonates etidronate and pamidronate. Gallium nitrate induced normocalcemia in 72% to 82% of patients; in contrast to the comparator agents, it was effective regardless of epidermoid tumor status. Epidermoid tumors are associated with high levels of parathyroid hormone-related protein (PTHrP), the principal mediator of cancer-related hypercalcemia in solid tumors. High levels of PTHrP appear to adversely impact the calcium-lowering potential of bisphosphonates. The recommended schedule of gallium nitrate for the treatment of cancer-related hypercalcemia is 200 mg/m2 per day as a 5-day continuous intravenous infusion, administered with adequate hydration and close monitoring of renal function. Gallium nitrate is an effective treatment option for moderate-to-severe cancer-related hypercalcemia, a setting in which morbidity and mortality are high.