The study of gemcitabine in combination with other chemotherapeutic agents as an effective treatment for prostate cancer.
BACKGROUND
Gemcitabine has demonstrated clinical activity against several common cancers. Our studies examine the ability of gemcitabine, both alone and in combination with other chemotherapeutic agents, to inhibit the in vitro and in vivo growth of several prostate cancer cell lines.


METHODS
Cultures of LNCaP, PC-3 or MLL cells were exposed to either gemcitabine or other appropriate agents for specified amounts of time. Cells were lysed and nuclei counted utilizing a Coulter Counter. For in vivo experiments, animals were injected with 1 x 10(5) MLL cells subcutaneously into the right flank. Animals were treated as indicated for 14 days. Tumors were then excised, weighed and measured.


RESULTS
In both human (PC-3 and LNCaP) and rat prostate (MLL) cancer cell lines our studies demonstrated gemcitabine had a strong effect in vitro, with an IC50 of approximately 500 nM in the human lines and 10 nM in MLL cells. In vivo, studies using the Dunning prostate cancer model in Copenhagen rats resulted in a dose response inhibition of tumor growth, with an 80% decrease in tumor size in rats treated with gemcitabine at 10 mg/kg.


CONCLUSIONS
Our results demonstrated the potent activity of gemcitabine against prostate cancer in the Dunning rat model and suggest the addition of paclitaxel may not aid in this activity.
Muenchen
H J
HJ
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
Quigley
M M
MM
Pilat
M J
MJ
Lehr
J E
JE
Brumfield
S K
SK
Mahoney
M
M
Pienta
K J
KJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D016190:Carboplatin / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D004357:Drug Synergism; D004961:Estramustine / Q000633:toxicity; D005047:Etoposide / Q000633:toxicity; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D004961:Estramustine; D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine