Phase I-II clinical trial with alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis.

Alpha-difluoromethylornithine (DFMO) is an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, the first enzyme in the synthesis of the polyamines putrescine, spermidine and spermine. DFMO has been shown to have a cytostatic and cytotoxic effect against various human tumor cell lines. The present study was designed to evaluate the toxicity and efficacy of this compound when administered orally at a dose of 1.7 g/m sq. t.i.d. added to conventional chemotherapy to 38 patients with carcinoma of the breast, stomach, prostate, female genital organs or metastatic carcinoma of unknown origin. A control group of 32 patients with similar malignancies received conventional chemotherapy only. Gastrointestinal, hematologic and biochemical abnormalities caused by DFMO were negligible. Reasonable ototoxicity was the major toxic effect caused by DFMO and resulted in discontinuation of therapy in 6 of 38 patients (15.8%). No differences in disease progression were seen between those patients receiving DFMO plus conventional chemotherapy and those receiving only conventional chemotherapy.