Enhanced activity of estramustine, vinblastine, etoposide, and suramin in prostate carcinoma.
Following hormonal therapy, few treatment regimens have activity in metastatic prostate cancer. Cytotoxic agents have minimal activity in this disease. However, combinations of cytotoxic agents may be beneficial. The activity of estramustine, vinblastine, etoposide, and suramin on cell growth was evaluated. Prostate specific antigen (PSA) is routinely used as a surrogate marker for disease progression. Many pharmacological agents alter PSA levels independently of their effect on tumor growth, the effect of these agents on PSA secretion was determined. Each agent was evaluated alone and in combination with the other drugs in two prostate cancer cell lines. In LNCaP cells, estramustine and suramin were cytostatic, while vinblastine and etoposide were cytotoxic. Estramustine down-regulated etoposide PSA secretion, while suramin had no effect. The effects of etoposide and vinblastine on PSA secretion were not evaluable. In PC-3 cells, only etoposide was cytotoxic. Tandem combinations were more cytotoxic than single agents in both cell lines. The addition of a third agent to the tandem combination produced less cytotoxicity. In our hands, the best combinations were estramustine/vinblastine, suramin/vinblastine, and suramin/etoposide. These combinations yielded 20-60% higher cytotoxicity than any of the drugs alone.
Arah
I N
IN
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
Dixon
S C
SC
Horti
J
J
Figg
W D
WD
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004961:Estramustine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013498:Suramin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage
D004961:Estramustine; D014747:Vinblastine; D013498:Suramin; D005047:Etoposide; D017430:Prostate-Specific Antigen