Gallium nitrate in the treatment of lymphoma

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.