Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment.
BACKGROUND
After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment.


METHODS
Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis.


RESULTS
ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone.


CONCLUSIONS
In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.
Brubaker
Kristen D
KD
Department of Biological and Allied Health Sciences, Bloomsburg University, Bloomsburg, PA, USA. kbrubake@bloomu.edu
Brown
Lisha G
LG
Vessella
Robert L
RL
Corey
Eva
E
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D004164:Diphosphonates / Q000627:therapeutic use*; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D043823:Taxoids / Q000627:therapeutic use*; D013977:Tibia; D014183:Transplantation, Heterologous; D000077211:Zoledronic Acid
D000972:Antineoplastic Agents, Phytogenic; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid