EVALUATION OF CONTINUOUS-INFUSION GALLIUM NITRATE AND HYDROXYUREA IN COMBINATION FOR THE TREATMENT OF REFRACTORY NON-HODGKINS-LYMPHOMA

Based on preclinical studies demonstrating synergy between gallium and hydroxyurea, we evaluated the efficacy and toxicity of continuous int ravenous gallium nitrate in combination with oral hydroxyurea in patie nts with refractory non-Hodgkin's lymphoma. Fourteen patients, median age 64 years (range 53-89), with stage III or IV low- or intermediate- grade lymphoma were treated with gallium nitrate and hydroxyurea in co mbination for 7 days at four different dose levels: (a) gallium nitrat e, 200 mg/m(2)/day; hydroxyurea, 500 mg/day; (b) gallium nitrate, 250 mg/m(2)/day; hydroxyurea, 1,000 mg/day; (c) gallium nitrate, 300 mg/m( 2)/day; hydroxyurea, 1,000 mg/day; and (d) gallium nitrate, 350 mg/m(2 )/day, hydroxyurea, 1,000 mg/day. All patients had progressive disease and had been heavily pretreated. Six of 14 patients had objective tum or regression following treatment (one complete response, one near-com plete response, and four partial responses) with a median duration of response of 7 weeks (range 3-38 weeks). An additional four patients ha d minor responses. Responses occurred at all dose levels and in both l ow- and intermediate-grade histologic subtypes. The predominant toxici ties encountered were anemia and reversible nephrotoxicity. Combinatio n gallium nitrate and hydroxyurea has significant activity in lymphoma and is well tolerated even by elderly patients. Because of the lack o f cross-resistance to other drugs and the potential synergistic antine oplastic activity, gallium nitrate and hydroxyurea should be further e valuated in combination with other chemotherapeutic agents.