title: Possible survival benefits from zoledronic acid treatment in patients with bone metastases from solid tumours and poor prognostic features-An exploratory analysis of placebo-controlled trials.
abstract: BACKGROUND
  Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials.
  
  
  METHODS
  Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models.
  
  
  RESULTS
  Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX (≥100 nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease.
  
  
  CONCLUSIONS
  These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD.
authors.affiliation: Department of Oncology, Cancer Clinical Trials Centre, University of Sheffield, Weston Park Hospital, Cancer Research Centre, Sheffield, UK.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.affiliation: Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Ker-Ai
authors.initials: KA
authors.lastname: Lee
authors.affiliation: Division of Urology, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montréal, QC, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Department of Oncology, Cancer Clinical Trials Centre, University of Sheffield, Weston Park Hospital, Cancer Research Centre, Sheffield, UK; Department of Oncology and Clinical Research, Cancer Research UK Centre, St James's Hospital, Leeds, UK.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Oncology, Division of Medical Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, ON, Canada.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Major
authors.affiliation: Division of Breast Oncology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Medicine, University Hospital Brugmann, ULB, Brussels, Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Body
keywords: Breast cancer; N-telopeptide of type I collagen; Non-small cell lung cancer; Prostate cancer; Survival; Zoledronic acid