Phase I clinical studies with gallium nitrate
Bedikian, A.Y.; Valdivieso, M.; Bodey, G.P.; Burgess, M.A.; Benjamin, R.S.; Hall, S.; Freireich, E.J.
Cancer Treatment Reports 62(10): 1449-1453
1978
ISSN/ISBN: 0361-5960 PMID: 361223 Document Number: 132412
Gallium nitrate, an anhydrous salt of gallium, had significant antitumor activity in animal tumor systems. A phase I clinical study of gallium nitrate was conducted in 42 patients with various types of solid tumors to evaluate its toxic effects and efficacy in man. The initial dose of 15 mg/m2 per day .times. 3 days repeated at 2 wk intervals was progressively increased to a maximum daily dose of 1350 mg/m2. Tumor regression .gtoreq. 50% was observed in 1 patient with lymphoma. Disease stabilization lasting .gtoreq. 4 wk was seen in 10 patients. There was no correlation between abnormal pretreatment gallium scans and tumor response to gallium nitrate. Impairment of renal function was dose-limiting and was manifested mainly by the occurrence of proteinuria and azotemia. Renal toxicity was more common at daily doses > 300 mg/m2 and appeared to be cumulative. Other toxic effects were nausea and vomiting, hearing loss, anemia, mucositis, metallic taste in the mouth and lethargy. Hematologic toxicity was minimal and was manifested mainly as anemia, which appeared to be dose-dependent. The administration of gallium nitrate was associated with significant leukocytosis secondary to granulocytosis. No significant changes in the absolute lymphocyte or platelet counts were noticed as a result of treatment with gallium nitrate. Doses of 300 mg/m2 per day .times. 3 days every 2 wk were well-tolerated. The lack of significant myelosuppressive toxicity makes this compound attractive for further clinical studies.