Urinary polyamine levels in cancer patients treated with D,L‐α‐Difluoromethylornithine, an inhibitor of polyamine biosynthesis

Abstract

The polyamine biosynthesis inhibitor D,L-alpha-Difluoromethylornithine hydrochloride monohydrate (DFMO) has cytostatic and cytotoxic effects against various human tumor cell lines in vitro. We measured levels of the polyamines putrescine and spermidine in the urine of cancer patients undergoing "conventional" chemotherapy in a two-arm randomized phase I-II study with and without additional DFMO administered orally at a dose of 1.7 g/sq.m. t.i.d. The study group included 38 patients with carcinoma of the breast, stomach, prostate, or female genital organs or metastatic carcinoma of unknown origin. A control group of 32 patients with similar malignancies received "conventional" chemotherapy without DFMO. Polyamine levels were determined periodically in the urine of all patients. In DFMO-treated patients, a significant decrease in putrescine and spermidine levels was observed after 3 weeks of DFMO therapy (the first time point evaluated) that usually persisted throughout the course of treatment. Significant differences in polyamine levels between DFMO-treated and control patients were observed for patients in remission. Less significant differences were noted, however, for patients with static or progressive disease between DFMO-treated and control groups. DFMO activity appears to be reflected by a long-term decrease in urinary polyamine levels.