Purpose: The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients.
Methods: This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan-Meier analyses.
Results: ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile.
Conclusions: This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC.
Keywords: AE, adverse events; BC, breast cancer; Bone marker; Bone metastases; CTX; CTX, C-terminal cross-linking telopeptide of type I collagen; Cancer; CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; EORTC, European Organisation for Research and Treatment of Cancer; ITT, intent-to-treat; NTX, urinary N-telopeptide; OPG, osteoprotegerin; P1NP; P1NP, amino-terminal propeptide of type I collagen; PC, prostate cancer; PSA, prostate-specific antigen; QoL, quality of life; RANKL, receptor activator of nuclear factor-κB ligand; SRE, skeletal-related event; ULN, upper limit of normal; VAS, visual analogue scale; ZOL, zoledronic acid; Zoledronic acid.