Low-dose gallium nitrate for prevention of osteolysis in myeloma: results of a pilot randomized study.

Abstract

Since osteolysis is a major cause of morbidity in myeloma, we conducted a pilot study to evaluate whether the addition of gallium nitrate to standard antimyeloma treatment could preserve or increase bone mass in patients with osteolytic disease. Patients stabilized on cytotoxic therapy were randomized to treatment with gallium nitrate for 6 months, or to observation only for the first 6 months followed by gallium nitrate treatment during the subsequent 6 months. Gallium nitrate was administered in monthly cycles by daily subcutaneous injections (30 mg/m2/d) for 2 weeks, followed by 2 weeks with no therapy, supplemented by an intravenous infusion (100 mg/m2/d) for 5 days every other month. Paired 6-month comparisons were available for seven observation periods and 13 gallium nitrate treatment periods. Total-body calcium assessed by delayed-gamma neutron activation (DGNA) decreased in four of seven patients during observation, but increased in nine of 13 patients during gallium nitrate treatment; the mean difference in total-body calcium (TBCa) between the two groups at 6 months was 3%. Median regional bone density assessed by dual-photon absorptiometry (DPA) declined by 1.4% in patients under observation (range, +6.7% to -18.3%), but was unchanged during gallium nitrate treatment (median change, 0%; range, -10.5% to +14.4%). The group mean vertebral fracture index assessed by lateral spine x-rays decreased by 27% during observation compared with 2% during gallium nitrate treatment. Mean body height decreased by 0.57 inches in the observation group and .06 inches in the gallium nitrate group. Patient self-assessment of bone pain showed that seven of 12 gallium nitrate-treated patients rated themselves as experiencing major reductions in bone pain, compared with zero of seven patients who were observed. One episode of hypercalcemia occurred in a patient under observation. Adjuvant treatment with low-dose gallium nitrate attenuates the rate of bone loss in myeloma and may be useful for ameliorating the consequences of skeletal morbidity in patients with cancer-related osteolysis.