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Gallium Nitrate for Advanced Paget Disease of Bone: Effectiveness and Dose-Response Analysis
- Raymond P. Warrell, Jr., MD;
- Barbara Bosco, RN;
- Stuart Weinerman, MD;
- Barbara Levine, PhD;
- Joseph Lane, MD; and
- Richard S. Bockman, MD, PhD
Abstract
Objective: To evaluate whether a brief course of treatment with gallium nitrate can reduce biochemical parameters of accelerated bone turnover in patients with advanced Paget disease.
Design: Unblinded trial, decreasing dose schedules of gallium nitrate.
Setting: University hospital with primary orthopedic and metabolic bone disease specialty.
Patients: Ten patients with advanced Paget disease who had previously received conventional therapy consisting of calcitonin, etidronate, or mithramycin.
Interventions: Five patients were entered into each of three dose schedules: 2. 5 mg/kg body weight per day by continuous intravenous infusion for 7 days; 0.5 mg/kg per day for 14 days by subcutaneous injection; and 0.25 mg/kg per day for 14 days by subcutaneous injection. Several patients were treated with different dose schedules. Patients were followed until relapse.
Results: Fifteen courses of treatment were administered to ten patients. Reductions in serum alkaline phosphatase and urinary hydroxyproline excretion were observed after treatment with each dose schedule. After treatment with high, intermediate, and low doses, the median maximum decreases in serum alkaline phosphatase activity were 49%, 39%, and 18%, respectively. The median maximum decreases in urinary hydroxyproline excretion were 50%, 52%, and 16%, respectively. The maximum decrease in urinary hydroxyproline excretion occurred within a median of 2 weeks from the start of treatment, whereas the maximum decrease in serum alkaline phosphatase activity occurred substantially later at a median of 6 weeks. All treatment schedules were well tolerated. Response duration was highly variable (range, 6 to 42 weeks).
Conclusions: Short-term treatment with gallium nitrate can reduce biochemical parameters of disease activity in patients with advanced Paget disease of bone. Larger trials using low-dose intermittent treatment schedules are required to evaluate the safety and effectiveness of this therapy.
Article and Author Information
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From the Hospital for Special Surgery; the Memorial Sloan-Kettering Cancer Center; and the Cornell University Medical College; New York, New York. For current author addresses, see end of text.
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Drs. Warrell and Bockman are co-patent holders on certain uses of gallium nitrate whose rights have been fully assigned to the Memorial Sloan-Kettering Cancer Center and licensed to Fujisawa Pharmaceutical Company. Drs. Warrell and Bockman have both subsequently acted as consultants to the company, and the company provided financial support to both Memorial Sloan-Kettering Cancer Center and the Hospital for Special Surgery to cover costs of the study.
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Grant Support: By grants CA-42445 and CA-38645 from the National Cancer Institute, DHHS; and by a grant from Fujisawa Pharmaceutical Company, Deerfield, Illinois.
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Requests for Reprints: Dr. Raymond P. Warrell, Jr., MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
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Current Author Addresses: Dr. Warrell: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
Drs. Weinerman, Levine, Lane, Bockman, and Ms. Bosco: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021.
- © 1990 American College of Physicians
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