The effect of alpha-difluoromethyl-ornithine on tumor growth, acute phase reactants, beta-2-microglobulin and hydroxyproline in kidney and bladder carcinomas.
Multiple oral doses of alpha-difluoromethyl-ornithine (alpha-DFMO), 18-24 g/day for up to 2 months, were administered to 2 patients with invasive and metastatic carcinoma of the bladder and to 3 patients with metastatic renal cancer in an open study. The moderate antigrowth effect of alpha-DFMO in these patients was concluded from the results of serial kidney, liver and bone scintigrams, from the low frequency of a local recurrence of bladder carcinoma and from the survival rate of 4 of 5 patients after 12 months. Increased excretion of hydroxyproline and beta2-microglobulin were measured 1 month following alpha-DFMO treatment suggesting initial tumor necrosis and degradation. Treatment was poorly tolerated with gastrointestinal side effects (e.g. gastritis, vomiting, diarrhea) in all subjects, erythropenia in 2 subjects (associated with thrombocytopenia and leucopenia in 1 subject each), and audiovestibular symptoms in 2 patients. All side effects were reversible and normal function returned 2-4 months after stopping therapy.
D015068:17-Ketosteroids / Q000652:urine; D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001609:Beta-Globulins / Q000652:urine*; D000518:Eflornithine; D004967:Estrogens / Q000652:urine; D005260:Female; D006242:Haptoglobins / Q000032:analysis; D006801:Humans; D006909:Hydroxyproline / Q000652:urine*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009952:Ornithine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065108:Ornithine Decarboxylase Inhibitors; D013739:Testosterone / Q000652:urine; D014168:Transferrin / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D000515:alpha 1-Antitrypsin / Q000032:analysis; D001613:beta 2-Microglobulin / Q000652:urine*
D015068:17-Ketosteroids; D000970:Antineoplastic Agents; D001609:Beta-Globulins; D004967:Estrogens; D006242:Haptoglobins; D065108:Ornithine Decarboxylase Inhibitors; D014168:Transferrin; D000515:alpha 1-Antitrypsin; D001613:beta 2-Microglobulin; D013739:Testosterone; D009952:Ornithine; D006909:Hydroxyproline; D000518:Eflornithine