The ZOTECT study: Effect of intravenous zoledronic acid on bone metabolism in patients with metastatic bone disease in prostate cancer (PC) and breast cancer (BC).

Abstract

4614 Background: Approximately 75% of patients (pts) with advanced BC or PC will develop bone metastases (BM), which influence bone metabolism and increase the incidence of skeletal related events (SREs). Therapy with zoledronic acid (ZOL) reduces the incidence and delays the onset of SREs. As recent studies showed strong correlations between the level of bone markers and SREs, the primary objective of this study was to access the course of several bone markers under therapy with ZOL and the correlation with disease outcomes. Methods: This prospective, single arm, open-label study investigated the effect of ZOL 4 mg IV q4wks given for 4 months on bone markers (CTX, PINP, RANKL, OPG) in PC and BC pts with BM. After 12 months a final follow-up was conducted. Secondary objectives included the relationship between metastatic sites assessed by bone scan and the level of bone markers at study entry, pain assessment (VAS) and analgesics score, the relationship between pain and SREs and the course of bone markers, SRE rate, quality of life (EORTC QLA-30/BR-23), Estradiol and PSA changes. Results: 99 BC pts and 301 PC pts were recruited at 98 German sites between May 06 and August 08. The course of OPG and RANKL was not significantly influenced by ZOL, however the level of PINP and CTX significantly decreased to stable values (p<0.0001). No significant differences between BC and PC pts were observed. Pts with high EOD (extension of disease) score had higher PINP and CTX baseline values and also showed a reduction in PINP and CTX. Average PSA values of PC pts were reduced from 168.5 to 92.5 µg/l. A total of 13 SREs occurred in 11 pts. Quality of life was not influenced under therapy. A slight pain reduction with correlation to the bone markers was detected. ZOL was generally well tolerated and adverse events were in accordance with the known safety profile of ZOL. Conclusions: 4 months therapy with ZOL significantly reduced the level of PINP and CTX in 400 BC and PC pts with BM. This result confirms the reduction of bone metabolism under ZOL resulting in prevention of SREs. This is the first study which investigated the effect of ZOL on OPG and RANKL and it showed no significant effect on these markers.