Treatment of androgen-independent prostate cancer using antimicrotubule agents docetaxel and estramustine in combination: an experimental study.
BACKGROUND
Estramustine in combination with other chemotherapeutic agents has demonstrated synergy in hormone-refractory prostate cancer. Docetaxel has demonstrated antineoplastic activity in a variety of chemotherapeutic-unresponsive tumors. We evaluated the effects of estramustine and docetaxel in preclinical models of prostate cancer.


METHODS
Cell viability of PC-3 and MAT-LyLu (MLL) cells were assessed 48 hr after drug treatment. For in vivo studies, each flank of five animals in six groups was injected with 1 x 10(6) MLL cells: control, estramustine, docetaxel (low- and high-dose), and low- and high-dose docetaxel with estramustine. Animals were treated on days 4 and 11, and sacrificed on day 14.


RESULTS
The IC(50) value for docetaxel was 2 nM in the PC-3 cells and 40 nM in the MLL cells. The addition of 100 nM of estramustine did not alter the IC(50) value for PC-3 cells. In the MLL cells, however, the IC(50) value was lowered to 15 nM. In vivo, low-dose docetaxel with estramustine demonstrated antineoplastic activity similar to that of high-dose docetaxel alone, suggesting additive activity between the drugs.


CONCLUSIONS
These results demonstrate that when used in combination, docetaxel and estramustine can be more effective at lower dosages than when the individual drugs are used alone.
Williams
J F
JF
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor 48109-9480, USA.
Muenchen
H J
HJ
Kamradt
J M
JM
Korenchuk
S
S
Pienta
K J
KJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008870:Microtubules / Q000187:drug effects; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects
D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D017239:Paclitaxel