Chemotherapy using docetaxel remains an important  therapy, despite the newly approved drugs, to treat hormone refractory prostate cancer. Chemotherapy improves survival, however, all men taking it will eventually become refractory to the treatment.

Zoledronic acid (ZA) is the most potent member of nitrogen-containing bisphosphonate family and has anti-tumor activity in prostate cancer. In a study, investigators evaluated whether ZA pretreatment enhances the cytotoxic and apoptotic effect of docetaxel in docetaxel resistant (Doc-R) prostate cancer cells.

Doc-R prostate cancer cells were pretreated with the increasing concentrations of ZA for 36 h and with the increasing concentrations of docetaxel for additional 36 h. Cell proliferation was then assessed.

The sequential treatment of 20 µM ZA followed by 10 nM docetaxel resulted in significantly enhanced cytotoxicity as compared to single agents alone in both at Doc-R prostate cancer cells. Moreover, docetaxel mediated DNA fragmentation and caspase 3/7 activity was increased by ZA pretreatment.

These findings strongly suggest that pretreatment with ZA enhances docetaxel-induced cytotoxicity and apoptosis in Doc-R prostate cancer cells. These preliminary results make ZA a good candidate for overcoming docetaxel resistance in prostate cancer.

J Clin Oncol 32, 2014 (suppl; abstr e16105): Zeki Surmeli, Emir Bozkurt, Ozge Ozer, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu, Burcak Karaca.

Joel T Nowak, M.A., M.S.W.