Therapie des Prostatakarzinoms mit Polyaminsyntheseinhibitoren

Abstract

The therapeutic concept of irreversible inhibition of both ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) by alpha-difluoromethylornithine (DFMO) and methylglyoxal bis-guanylhydrazone (MGBG) is based on pathologic activities of these enzymes in tumor tissue. The polyamines putrescine, spermidine and spermine are measured in highest concentration in the prostate of both men and animals, with a significant increase of spermine in benign hyperplasia of the prostate. Patients with metastatic cancer of the prostate have elevated putrescine levels in the 24-hour urine. Treatment with 3 or 1% DFMO or 11 mg/kg MGBG in transplantable human and experimental cancer of the prostate demonstrated a significant anti-growth effect. A combination of DFMO and MGBG is tumor-destructive. The combination of 1% DFMO and 11 mg/kg MGBG distinctly reduces the activity of ODC and SAMDC and significantly lowers the levels of putrescine, spermidine and spermine in the tumor.