Treatment of patients with advanced malignant lymphoma using gallium nitrate administered as a seven-day continuous infusion.
Previous trials of gallium nitrate (NSC-15200) showed that bolus administration produced dose-limiting nephrotoxicity without substantial antitumor activity. As an effort to increase the therapeutic index of this compound and to establish a satisfactory out-patient schedule, the authors evaluated the effects of gallium nitrate administered as a continuous infusion in patients with advanced malignant lymphoma. In an initial Phase I trial, four dose levels which ranged from 200 to 400 mg/m2/day in 27 patients were studied. Nausea which impaired oral hydration was found to be dose-limiting. A dose of 300 mg/m2/day was chosen for extended Phase II evaluation and 37 additional patients were entered into the study at that dose level. Overall, 16 of 47 patients (34%) who had bi-dimensionally measurable parameters of disease achieved major antitumor responses (six of 15 with diffuse "histiocytic" lymphoma, five of ten with diffuse poorly-differentiated lymphocytic lymphoma, two of five with nodular poorly-differentiated lymphocytic lymphoma, and three of 17 with Hodgkin's disease). The median duration of response was 2.5 months. Only 8% of patients who received 300 mg/m2/day developed an increase in serum creatinine concentration greater than 1.1 mg/dl over baseline values. Hypocalcemia occurred in two-thirds of patients. Other toxic effects, including paresthesiae, diarrhea, and hearing loss, were noted in less than 5% of patients. There was minimal myelosuppression. The authors conclude that gallium nitrate administered as a continuous infusion for seven days at 300 mg/m2/day is well-tolerated and effective treatment for patients with advanced malignant lymphoma. Outpatient administration using portable infusion pumps is safe and practical. Further evaluation of the drug administered as a constant infusion is indicated in patients with other neoplastic diseases.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005708:Gallium / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D007263:Infusions, Parenteral; D007674:Kidney Diseases / Q000139:chemically induced; D008171:Lung Diseases / Q000139:chemically induced; D008223:Lymphoma / Q000188:drug therapy*; D008875:Middle Aged
D000970:Antineoplastic Agents; D003404:Creatinine; D005708:Gallium; C027235:gallium nitrate