Gallium nitrate was originally developed as an
antineoplastic agent; however, further studies have revealed that this
drug has extremely potent effects on turnover of bone, and that low doses can be used to reduce
bone resorption. Like the
bisphosphonates,
gallium nitrate has been studied in both malignant and in nonmalignant conditions. The results of randomized double blind studies have suggested that this
drug has superior clinical efficacy relative to
etidronate,
calcitonin, and
pamidronate for the acute control of
cancer-related
hypercalcemia. In patients with Paget's disease, low doses of
gallium nitrate reduce biochemical parameters of accelerated bone turnover, including urinary excretion of
calcium,
hydroxyproline, and urinary
collagen cross-linked N-telopeptides. Preliminary studies showed similar effects in patients with bone involvement from a wide variety of
tumor types. Based on this high degree of clinical potency revealed in clinical studies, two randomized Phase III studies have been initiated in patients with bone
metastases from
breast carcinoma and bone involvement due to
multiple myeloma. Both studies employ cyclic
therapy with low dose
gallium nitrate (i.e., 40 mg administered as a
subcutaneous injection once daily for 2 weeks, followed by 2 weeks off treatment, recycled monthly). The endpoints of both studies are to document reductions in time to "morbid skeletal events," such as palliative skeletal
radiotherapy, stabilizing
orthopedic surgery, or
pathologic fractures, as well as decreases in
pain and
analgesic requirements and improvements in mobility and other aspects of quality of life. These trials should provide definitive evidence of whether this agent is safe and effective as a treatment for bone
metastases.