MULTICENTER TRIAL OF LOW-DOSE GALLIUM NITRATE IN PATIENTS WITH ADVANCED PAGETS-DISEASE OF DONE

Gallium nitrate is a potent antiresorptive drug that has been extensiv ely tested in patients with accelerated bone turnover. We have evaluat ed the effects of this new agent in a pilot multicenter trial of 49 pa tients with advanced Paget's disease of bone. Patients were randomized to receive 0.05, 0.25, or 0.5 mg/kg.day gallium nitrate administered by sc injection in two 14-day cycles. Serum alkaline phosphatase, fast ing 2-h urinary hydroxyproline and N-telopeptide collagen cross-links excretion, and quality of life were assessed every 2 weeks for 12 week s. The group mean alkaline phosphatase activity at baseline was 854 +/ - 100 (+/- SEM) IU/L. The mean changes from baseline to week. 12 in se rum alkaline phosphatase were +0.5%, -24%, and -31%, respectively, for the three doses tested. The differences for each of the higher dose l evels (0.25 and 0.5 mg/kg.day) was statistically significant (P less t han or equal to 0.05), and nearly half of the patients treated with th e 0.5 mg/kg.day dose achieved a 50% or more reduction in enzyme activi ty. The nadir value in hydroxyproline excretion occurred at 10 weeks, with mean changes of +9%, -10%, and -17% for the 0.05, 0.25, and 0.5 m g/kg.day doses, respectively; the difference was significant only at t he 0.5 mg/kg.day level (P < 0.01). Urinary collagen cross-link excreti on showed a significant decrease at the 0.25 and 0.5 mg/kg.day doses. We also observed a definite, but nonsignificant, trend for improved qu ality of life in patients treated at the highest drug dose. Minor disc omfort at the injection site was frequently reported, but did not lead to interruption of therapy. Our results in these patients who had rec eived moderate to extensive prior therapies with other drugs show that cyclical, low dose, sc administration of gallium nitrate is safe and effective for treating patients with advanced Paget's disease of bone.