Study Objective: To determine whether gallium nitrate therapy is superior to maximally approved doses of calcitonin for acute control of cancer-related hypercalcemia.
Design: Randomized, double-blind comparison of active treatments.
Setting: Comprehensive cancer center.
Patients: One hundred ninety-eight consecutive hypercalcemic events in 164 patients screened for entry. Eligibility criteria: hospitalization and intravenous hydration for at least 2 days; persistent elevated serum calcium levels of 2.99 mmol/L or greater (adjusted for serum albumin); serum creatinine levels of 221 µmol/L or less; no cytotoxic chemotherapy, radiation, or mithramycin within the preceding 7 days or during study; no concurrent use of aminoglycoside antibiotics; life expectancy greater than 4 weeks; lymphoma and parathyroid carcinoma excluded. Patients were stratified by histologic type of tumor (epidermoid or nonepidermoid). Fifty patients were randomized and treated.
Interventions: Gallium nitrate 200 mg/m2 body surface area for 5 days by continuous intravenous infusion, or salmon calcitonin 8 IU/kg body weight every 6 hours for 5 days by intramuscular injection. Patients randomized to receive gallium nitrate received sham injections of saline to simulate calcitonin; patients randomized to receive calcitonin received 1000 mL 5%-dextrose solution to simulate gallium nitrate.
Measurements and Main Results: All patients were evaluable. Eighteen of twenty-four patients who received gallium nitrate achieved normocalcemia compared with 8 of 26 patients who received calcitonin for an observed difference of 44% (95% confidence interval, 19% to 69%; P = 0.002). Median duration of normocalcemia before other cytotoxic or hypocalcemic therapy was 6 days for patients treated with gallium nitrate compared with 1 day for patients treated with calcitonin (P < 0.001). Median duration of normocalcemia regardless of intercurrent treatment and without adjustment for serum albumin was 11+days for patients treated with gallium nitrate and 2 days for patients treated with calcitonin (P < 0.01). Mean daily fluid intake and mean daily dose of furosemide were similar in both treatment groups. No additional benefit was seen in 9 patients randomized to receive calcitonin who incidentally received corticosteroids.
Conclusions: Gallium nitrate therapy is highly effective and superior to maximally approved doses of calcitonin for acute control of cancer-related hypercalcemia.