Inhibition of prostate cancer growth by 9-aminocamptothecin and estramustine.
OBJECTIVE
Hormone-refractory prostate cancer continues to be associated with a very poor prognosis. Agents that interact with the nuclear matrix have been demonstrated to have activity against hormone-refractory prostate cancer. It was the aim of this study to assess the activity of estramustine, an estradiol-nitrogen mustard conjugate, and 9-aminocamptothecin (9-AC), a topoisomerase I inhibitor, in a preclinical model of hormone-refractory prostate cancer.


METHODS
We used the Dunning rat prostatic adenocarcinoma model to demonstrate that the combination of estramustine and 9-AC interacts at the level of the nuclear matrix to inhibit the growth of prostate cancer cells.


RESULTS
We demonstrate that the combination of these two agents at pharmacologically achievable doses are cytotoxic to rat and human prostate cancer cells in vitro and in vivo in the rat.


CONCLUSIONS
The combination of the two drugs was significantly more cytotoxic than either drug alone. We have instituted a Phase II clinical trial in patients with hormone-refractory prostate cancer using 9-AC based on these preclinical findings.
Naik
H
H
Michigan Prostate Institute, University of Michigan Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor 48109-0680, USA.
Lehr
J E
JE
Pienta
K J
KJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004961:Estramustine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
D018931:Antineoplastic Agents, Hormonal; D004961:Estramustine; C080125:9-aminocamptothecin; D002166:Camptothecin