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.