GALLIUM NITRATE FOR THE TREATMENT OF BONE METASTASES

Gallium nitrate was originally developed as an antineoplastic agent; h owever, further studies have revealed that this drug has extremely pot ent effects on turnover of bone, and that low doses can be used to red uce bone resorption. Like the bisphosphonates, gallium nitrate has bee n studied in both malignant and in nonmalignant conditions. The result s of randomized double blind studies have suggested that this drug has superior clinical efficacy relative to etidronate, calcitonin, and pa midronate for the acute control of cancer-related hypercalcemia. In pa tients with Paget's disease, low doses of gallium nitrate reduce bioch emical parameters of accelerated bone turnover, including urinary excr etion of calcium, hydroxyproline, and urinary collagen cross-linked N- telopeptides. Preliminary studies showed similar effects in patients w ith bone involvement from a wide variety of tumor types. Based on this high degree of clinical potency revealed in clinical studies, two ran domized Phase III studies have been initiated in patients with bone me tastases from breast carcinoma and bone involvement due to multiple my eloma. Both studies employ cyclic therapy with low dose gallium nitrat e (i.e., 40 mg administered as a subcutaneous injection once daily for 2 weeks, followed by 2 weeks off treatment, recycled monthly). The en dpoints of both studies are to document reductions in time to ''morbid skeletal events,'' such as palliative skeletal radiotherapy, stabiliz ing orthopedic surgery, or pathologic fractures, as well as decreases in pain and analgesic requirements and improvements in mobility and ot her aspects of quality of life. These trials should provide definitive evidence of whether this agent is safe and effective as a treatment f or bone metastases. (C) 1997 American Cancer Society.