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.