Evaluation of weekly escalating doses of dichloromethotrexate in patients with hepatocellular carcinoma and other solid tumors

• Published in: Cancer chemotherapy and pharmacology 1982-01, Vol.8 (3), p.305
• Main Authors: Tester, W J, Donehower, R C, Eddy, J L, Myers, C E, Ihde, D C
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - administration & dosage; Carcinoma, Hepatocellular - drug therapy; Drug Administration Schedule; Female; Humans; Liver Neoplasms - drug therapy; Male; Methotrexate - administration & dosage; Methotrexate - adverse effects; Methotrexate - analogs & derivatives; Methotrexate - metabolism; Middle Aged; Protein Binding; Serum Albumin - analysis
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00254055

Twenty-one patients with solid tumors were treated with weekly 6-h intravenous infusions of dichloromethotrexate (DCM), with escalating doses every other week. Frequently observed toxicities included leukopenia, thrombocytopenia, and mucositis. Nausea, vomiting, diarrhea, and elevation of hepatic enzymes and bilirubin occurred less often. The toxicity of DCM was dose-dependent; the maximum tolerated dosage excalation plan was 400 mg/m2 x 2 weeks, 800 mg/m2 x 2 weeks, and then 1,200 mg/m2 weekly. Plasma concentrations of DCM were measured during 61 infusions and apparent half-lives determined. The plasma elimination of DCM appears to be similar to that of methotrexate. Three objective tumor responses seen in the seven hepatocellular carcinoma patients treated warrant further investigation.