[Therapy with inhibitors of polyamine biosynthesis in refractory prostatic carcinoma. An experimental and clinical study].
Transplantable prostate adenocarcinoma were treated with polyamine biosynthetic inhibitors. alpha-difluoromethylornithine (alpha-DFMO), an inhibitor of ornithine decarboxylase and by s-methylglyoxal-bisguanylhydrazone (MGBG), an inhibitor of s-adenosylmethionine decarboxylase. The therapeutic regimen of 0.8-1.11 g/kg DFMO reduced the tumor growth by 40% whilst the combination with 10.5 mg/kg MGBG completely destroyed the prostate adenocarcinomas in the tumor-bearing animals. The polyamine content of spermidine and spermine in the cancerous tissues is significantly lower whereas the putrescine levels remain unchanged. The MGBG therapy distinctly stimulates the activity of ornithine decarboxylase and increases the putrescine concentration up to toxic levels. The application of alpha-DFMO prevented the toxic accumulation of putrescine and allowed higher doses of MGBG. Clinical trials with polyamine antimetabolites appeared useful due to pathological polyamine excretion of patients with metastatic prostate cancer. The therapy with 0.2-0.3 g/kg DFMO in patients with hormone-resistent prostate cancer and metastasis displayed a moderate anti-tumor activity following 2 months additional treatment. High levels of side effects, however, were registered and were similar to those of other cytotoxic compounds. A combined therapy with DFMO/MGBG in a patient with metastatic anaplastic prostate cancer did not improve the survival rate but showed regressive effects of the histological pattern.
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D000230:Adenocarcinoma / Q000032:analysis / Q000188:drug therapy* / Q000652:urine; D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002277:Carcinoma / Q000188:drug therapy*; D000518:Eflornithine; D004967:Estrogens / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008935:Mitoguazone / Q000009:adverse effects / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D009952:Ornithine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065108:Ornithine Decarboxylase Inhibitors; D011470:Prostatic Hyperplasia / Q000652:urine; D011471:Prostatic Neoplasms / Q000032:analysis / Q000188:drug therapy* / Q000652:urine; D011472:Prostatitis / Q000652:urine; D011700:Putrescine / Q000032:analysis / Q000652:urine; D051381:Rats; D013095:Spermidine / Q000032:analysis / Q000652:urine; D013096:Spermine / Q000032:analysis / Q000652:urine
D000970:Antineoplastic Agents; D004967:Estrogens; D065108:Ornithine Decarboxylase Inhibitors; D013096:Spermine; D009952:Ornithine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine
Therapie mit Inhibitoren der Polyaminbiosynthese beim refraktären Prostatakarzinom. Eine experimentelle und klinische Studie.