Markers of bone metabolism predict survival in hormone refractory prostate cancer (HRPC): Results from a randomized California Cancer Consortium & University of Chicago trial.

4569 Background: Bone metabolism is characterized by bone formation (osteoblasts) and resorption (osteoclasts). Bone mass is dependent on the balance of these activities. In metastatic PC, osteoblasts predominate, leading to sclerotic bone mets. Although biochemical markers of bone metabolism have been evaluated in metastatic PC, they have not been established as prognostic or predictive variables. As part of a randomized phase II trial of 2 doses of the matrix metalloproteinase inhibitor BMS-275291 (Arm A: 1200 vs. Arm B: 2400 mg) in HRPC patients (pts) with bone mets, markers of bone turnover were prospectively assessed and correlated with pt outcome.,Markers of bone formation (osteocalcin [OCN], procollagen N-terminal propeptides: PINP & PIIINP) and resorption (N-telopeptide [NTX], pyridinoline [PYD], deoxypyridinoline [DPD]) in plasma were assayed using commercial enzyme immunoassays. Marker values were dichotomized at the median and correlated with overall (OS) and progression-free survival (PFS) by log-rank.,80 pts were randomized. 4-month (mo) PFS favored Arm A (24% vs. 10%, p=0.009). OS was similar in both arms. 69 pts had evaluable baseline plasma specimens. Due to early progression, only 34 had serial plasma obtained. All markers reported are baseline values. NTX ≤ 14.4 nM had better OS [median survival (MS) not reached vs. 10.7 mos, p<0.0001] & 4-mo PFS (10% vs 22%, p=0.04). OCN > 0.89 ng/mL had better 4-mo PFS (12% vs 20%, p=0.01). PINP and PIIINP < the medians (86.5 & 5.6 ng/mL, respectively) had better OS (MS not reached vs. 12 mos; p<0.0001 and 0.005, respectively) and 4-mo PFS (9% vs. 22%, p=0.02 and p=0.01, respectively). DPD < 57 nmol/dL had better OS (MS not reached vs. 12 months, p=0.0002) and 4-mo PFS (9% vs 25%, p=0.04). Log of PIIINP & PINP predicted survival in a multivariate Cox model (p<0.00002 for the 2-variable model). Bisphosphonate use (23 pts) did not interact with assay results in predicting survival.,Baseline levels of bone metabolism markers have prognostic value in HRPC pts with bone mets. Prospective validation in the phase III setting is planned. (NOI CM17101, CM17102; VANCHCS & ACS-CRTG to PNL). No significant financial relationships to disclose.