Preliminary studies have shown that gallium nitrate is effective treatment for cancer-related hypercalcemia, and that this effect is due to inhibition of calcium release from bone. In vivo studies in animals have also established that treatment with gallium nitrate increases the amount of calcium in bone. The dual effects of inhibiting bone resorption and increasing calcium accretion into newly-mineralized bone suggest that gallium nitrate will be useful for other diseases characterized by loss of bone mass, particularly cone metastases. First, we intend to establish that clinical treatment with gallium nitrate effectively reduces biochemical parameters of bone turnover in cancer patients with bone metastases. Second, since gallium must currently be administered by i.v. infusion, chronic administration would be considerably facilitated by development of a subcutaneous (SQ) route. We will perform a toxicologic study of the SQ route in rodents which will allow the use of this injection method in humans. Subsequently, a bioavailability and pharmacokinetic study of subcutaneously administered gallium nitrate will be conducted. Third, gallium nitrate will be administered over a 6 month period to a selected group of cancer patients who have disease primarily limited to bone. This study is intended to demonstrate that chronic treatment with gallium nitrate increases the mineral content of bone at both disease-involved and uninvolved sites. A positive result from these pilot studies will serve as a basis for a randomized study of gallium nitrate vs. placebo as adjuvant treatment for patients with bone metastasis. Documentation of this novel use for a drug which both retards bone resorption and increases calcium accretion into bone would be expected to reduce bone pain and fractures which are a major source of morbidity in cancer patients with bone metastasis.
