Effect of zoledronic acid (ZA) versus placebo on bone mineral density (BMD) in androgen-deprived prostate cancer patients with and without bone metastases (mets)

Abstract

4760 Background: Bisphosphonates can prevent BMD loss in prostate cancer patients receiving androgen deprivation. Previous studies of ZA and BMD in this population excluded patients with bone mets because of concern that mets may interfere with DEXA results. Methods: We performed a double-blind, placebo-controlled, randomized study of ZA in prostate cancer patients with and without bone mets on androgen deprivation for < 12 months. Patients were randomized to receive either 4 mg ZA or normal saline placebo IV every 3 months for 4 treatments. BMD of the femoral neck (FN) and lumbar spine (LS) were measured by DEXA at 0, 3, 6, 9, and 12 months. Results: From 1/00 through 12/02, 42 of a planned 80 patients were randomized. Accrual was stopped due to initiation of a multi-center study that is currently ongoing. BMD data are available for 18 patients who received placebo and 21 who received ZA. Baseline characteristics were well-balanced between the 2 groups (placebo vs. ZA): mean FN BMD 0.998 g/cm2 (SD 0.126) vs. 0.979 g/cm2 (SD 0.196); mean LS BMD 1.385 g/cm2 (SD 0.274) vs. 1.344 g/cm2 (SD 0.207). 9 patients in each arm had bone mets detected by bone scan. A random effect model was used to examine change in BMD over one year. The mean change in BMD per year (slope, g/cm2/year) is shown in the table below. Results are shown for all patients and for patients excluded based on bone scan abnormalities detected in the region of BMD measurement. Conclusions: When all patients were analyzed, no statistically significant difference in the mean change per year of BMD was detected. When patients with scintigraphic evidence of bone mets at the site of DEXA measurement were excluded, the expected benefit of ZA therapy became apparent. Mets detected in the region of DEXA measurement can interfere with interpretation of ZA effect. Bone marker analysis for this study is pending. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis