Reviewer's report Administration of Zoledronic Acid Enhances the Effects of Docetaxel on Growth of Prostate Title: Cancer in the Bone Environment

General This manuscript by Brubaker and colleagues reports the investigation of the effects of docetaxel (20 mg/kg every 2 weeks) alone or in combination with the bisphosphonate zoledronic acid (0.1 mg/kg, given s.c. twice weekly) on the in vivo growth of prostate cancer LuCaP 23.1 tumors in bone. These authors have previously shown that zoledronic acid (0.25 mg/kg, given s.c. twice weekly) reduces the formation of osteoblastic lesions induced by LuCaP 23.1 cells and decreases tumor burden in the bones of animals (Corey et al., Clin Cancer Res, 2003). Others have shown that zoledronic acid (0.025 mg/kg, s.c. twice daily) alone or in combination with paclitaxel (8 mg/kg, once weekly) reduces the formation of osteolytic lesions caused by PC-3MM2 prostate cancer cells and decreases skeletal tumor burden (Kim et al., Cancer Res 2005). The present study is the first to describe the effects of a combined treatment of zoledronic acid with docetaxel on the formation of prostate cancer osteoblastic lesions and skeletal tumor growth. Based on a series of in vivo and in situ studies, the investigators conclude that zoledronic acid enhances the antitumor effect of docetaxel on growth of LuCaP 23.1 prostate cancer cells in bone. While experiments conducted by the investigators largely support this conclusion, there are some issues that need to be further addressed and/or clarified.