title: The ZOTECT study: Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Philipps-University of Marburg, Universitatsklinikum Giessen und Marburg, Marburg, Germany.
authors.forename: Peyman
authors.initials: P
authors.lastname: Hadji
authors.affiliation: Philipps-University of Marburg, Universitatsklinikum Giessen und Marburg, Marburg, Germany.
authors.forename: May
authors.initials: M
authors.lastname: Ziller
authors.affiliation: Urologische Klinik, Klinikum rechts der Isar der Technische Universitaet Muenchen, Muenchen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Urologische Klinik, Klinikum rechts der Isar der Technische Universitaet Muenchen, Muenchen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Autenrieth
authors.affiliation: Novartis Pharma GmbH, BU Oncology, Nuernberg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Muth
authors.affiliation: Novartis Pharma GmbH, BU Oncology, Nuernberg, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Ruebel
authors.affiliation: Novartis Pharma GmbH, Biostatistics and Medical Writing, Nuernberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: May
authors.affiliation: Novartis Pharma GmbH, BU Oncology, Nuernberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Birkholz
authors.affiliation: Outpatient Center, Magdeburg, Germany.
authors.forename: Erhardt
authors.initials: E
authors.lastname: Diebel
authors.affiliation: Outpatient Center, Magdeburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Gleissner
authors.affiliation: Outpatient Center, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rothe
authors.affiliation: Urologische Klinik, Klinikum rechts der Isar der Technische Universitaet Muenchen, Muenchen, Germany.
authors.forename: Juergen E
authors.initials: JE
authors.lastname: Gschwend
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