title: Evaluation of continuous-infusion gallium nitrate and hydroxyurea in combination for the treatment of refractory non-Hodgkin's lymphoma.
abstract: Based on preclinical studies demonstrating synergy between gallium and hydroxyurea, we evaluated the efficacy and toxicity of continuous intravenous gallium nitrate in combination with oral hydroxyurea in patients 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 combination for 7 days at four different dose levels: (a) gallium nitrate, 200 mg/m2/day; hydroxyurea, 500 mg/day; (b) gallium nitrate, 250 mg/m2/day; hydroxyurea, 1,000 mg/day; (c) gallium nitrate, 300 mg/m2/day; hydroxyurea, 1,000 mg/day; and (d) gallium nitrate, 350 mg/m2/day, hydroxyurea, 1,000 mg/day. All patients had progressive disease and had been heavily pretreated. Six of 14 patients had objective tumor regression following treatment (one complete response, one near-complete response, and four partial responses) with a median duration of response of 7 weeks (range 3-38 weeks). An additional four patients had minor responses. Responses occurred at all dose levels and in both low- and intermediate-grade histologic subtypes. The predominant toxicities encountered were anemia and reversible nephrotoxicity. Combination gallium nitrate and hydroxyurea has significant activity in lymphoma and is well tolerated even by elderly patients. Because of the lack of cross-resistance to other drugs and the potential synergistic antineoplastic activity, gallium nitrate and hydroxyurea should be further evaluated in combination with other chemotherapeutic agents.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, U.S.A.
authors.forename: C R
authors.initials: CR
authors.lastname: Chitambar
authors.forename: S A
authors.initials: SA
authors.lastname: Zahir
authors.forename: P S
authors.initials: PS
authors.lastname: Ritch
authors.forename: T
authors.initials: T
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D005260:Female; D005708:Gallium / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D005708:Gallium; C027235:gallium nitrate; D006918:Hydroxyurea