Gallium nitrate is effective and well tolerated for the treatment of
cancer-related
hypercalcemia. At somewhat higher doses,
gallium nitrate also has cytotoxic activity against a variety of
cancers. The probable mechanism is inhibition of both
ribonucleotide reductase and a
protein tyrosine phosphatase. Radioactive
gallium ((67)Ga) is concentrated at sites of
malignant lymphoma,
Hodgkin's disease, and other
tumors.
Gallium nitrate has substantial single-agent activity in the treatment of patients with advanced
lymphoma and has also shown activity when used in combination with other agents. Significant response rates have been observed in patients with
diffuse large cell lymphoma,
small lymphocytic lymphoma, and
follicular lymphoma. Because of its unique mechanism of action,
gallium nitrate could be non-cross-resistant with many of the
cytotoxic agents used as standard
chemotherapy for
non-Hodgkin's lymphoma. Nephrotoxicity, the most frequent adverse event associated with
gallium nitrate, can generally be minimized by ensuring adequate oral hydration and avoiding concomitant use of other nephrotoxic drugs.
Gallium nitrate causes little myelosuppression and is therefore well tolerated by patients with advanced disease who have received extensive prior
therapy. Given its unique mechanism of action, the high level of single-agent activity in published clinical trials, the absence of significant myelosuppression, and the potential lack of cross-resistance, further clinical study of
gallium nitrate both alone and in combination with other active agents is warranted.