There is a rapid increase in the incidence of AIDS-related non-Hodgkin's lymphoma (NHL). The histologic types of NHL which predominates in AIDS patients include the high grade B-cell types including large cell immunoblastic and small non-cleaved cell lymphoma (70% of AIDS related lymphoma) and the intermediate grade diffuse large cell lymphoma making up the remaining 30%. Non-Hodgkin's lymphoma in the patients with AIDS is difficult to treat. The tumor is usually histologically high grade with multiorgan and central nervous system involvement. The patients usually have a compromised bone marrow. First line, aggressive NHL regimens are frequently, inactive. The first Specific Aim of the present proposal is to determine the phase II activity of the agent gallium nitrate in patients with AIDS-related NHL who have failed treatment with a first line chemotherapy regimen. Gallium nitrate is attractive as a candidate to treat these patients because: l) it has had antitumor activity in patients with non-AIDS related NHL; 2) it is non-myelosuppressive 3) it concentrates in lymphoma tissue and 4) it has excellent penetration through the blood-brain barriers. In the present study we will utilize gallium niturate on a schedule of 350 mg/m2/day as a continuous infusion x 5 days. This schedule is utilized to maximum efficacy and minimize toxicities. The trial is designed to detect the true response rate in patients with AIDS-related NHL as well as to determine the incidence of toxicities of gallium nitrite in these patients. In addition the clinical pharmacology of gallium nitrate will be explored. Based on the characteristics of gallium nitrate we believe the agent has an excellent chance of being active in patients with AIDS-related NHL.
