5161 Background: The primary objective of this study is to examine the pharmacodynamic effects of two different regimens of zoledronic acid, Orazol 20 mg tablets versus Zometa 4mg IV infusion once-monthly therapy on biomarkers in male bisphosphonate-naïve hormone-refractory prostate cancer patients. Methods: The study is an open-label, multi-center phase II clinical trial to compare oral Orazol 20 mg tablets weekly, to infusions of intravenous Zometa 4mg monthly, in males with hormone-refractory prostate cancer, bone metastases, and no prior bisphosphonate treatment. Patients were assigned into one of three cohorts. The three treatments administered were IV Zometa, 4 mg, 15 minute infusion, Day 0 and Day 28; Orazol po, 20 mg, Days 0, 7, 14, 21, 28, 35, 42, and 49; and Orazol po, 20 mg, Days 0, 1, 2, 3, 28, 35, 42, and 49. The study population consisted of men with hormone refractory prostate cancer as evidenced by history of rising PSA levels (last 2 of 3 PSA levels must be above nadir), who are bisphosphonate-naive, and have radiographically-confirmed bone metastases. Efficacy assessments: The primary endpoints are the assessment of response of four biomarkers, urinary NTX, serum CTX, serum bone specific alkaline phosphatase, and serum calcium on days -7, 0, 7, 14, 21, 28, 35, 42, 49, and 56. Secondary endpoints are assessments of performance and pain scores based on ECOG performance status, BPI, and analgesic use. Safety assessments include physical examinations, vital signs and body weight, hematology panel, urinalysis, and blood chemistry panel. Results: The results demonstrated a rapid decrease for all four biomarkers. This decrease was seen at seven days, and was sustained throughout the study. There were no statistically significant differences between any of the treatments in the primary and secondary endpoints. Conclusions: From the results of MER-101–03, Orazol weekly therapy appears to be as effective as Zometa, based on the biomarkers analyzed. Orazol offers a substantial improvement in therapy over IV infusion for patients, with efficacy that is at least comparable based on the results obtained here. No significant financial relationships to disclose.
Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases
