Relationship of urinary polyamines to tumor activity and tumor volume in patients.

Serially obtained urinary polyamine levels were determined for 192 patients during a specified time period. The number of patient urine samples totaled 938. The patients had tumors of either the breast, stomach, prostate, or female genital tract, or metastatic carcinomas of unknown origin. Tumor activity and tumor volume, along with other clinical information, were also recorded during the time period. Possible associations between tumor activity and tumor volume on one hand, and polyamine levels on the other hand, were explored via different statistical analyses. For each tumor type, statistically significant group differences were found in polyamine levels between patients with nonactive tumors and patients with active large tumors. Predictive values of polyamine assays for change in disease activity and stability in disease nonactivity for tumors of the breast, female genital tract, and prostate were also computed. For breast tumors, these predictive values do not support the clinical utility of the use of polyamine levels to monitor disease states. For tumors of the female genital tract and prostate, these predictive values yield an indeterminant conclusion.

Further evidence for the use of polyamines as biochemical markers for malignant tumors.

One hundred ninety patients with a variety of tumor presented within a specified time period and fit a specified protocol. Multiple serial urinary putrescine, spermidine, and spermine levels were obtained in these patients, and their disease activity over time, defined as either active or nonactive, was determined by clinical examination, the results of laboratory tests, and radiological criteria. Twenty-four-hr urine collections were used for analysis of polyamine levels. A linear mixed-effects model and the method of maximum likelihood estimation were used for statistical analysis. Statistically significant differences were found in polyamine levels between patients with active or nonactive disease for tumors of the breast, stomach, prostate, female genital tract, and a variety of metastatic carcinomas of unknown origin. There were 105 patients with these tumors; 319 polyamine determinations were obtained from this subset of patients. Our results suggest that serial determination of polyamine levels in urine may have clinical utility for monitoring the disease states for these tumors.

Urinary polyamine levels in cancer patients treated with D,L-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis.

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.