The study of gemcitabine in combination with other chemotherapeutic agentsas 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 vi tro and in vivo growth of several prostate cancer cell lines. Materials and Methods: Cultures es of LNCaP, PC-3 or MLL cells were exposed to either ge mcitabine ol other appropriate agents for specified amounts of lime. Cells were lysed and nuclei counted utilizing a Coulter Counter For in vivo exper iments, animals were injected with I 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 gemcit abine 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 cancel model in Copenhagen rats resulted in a dose response inhib ition of tumor growth, with an 80% decrease in tumor size in rats treated w ith gemcitabine at 10 mg/kg. Conclusions: Our results demonstrated the pote nt activity of gemcitabine against prostate cancer in the Dunning rat model and suggest the addition of paclitaxel may not aid in this activity.