title: Phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal-related event or progressive bone metastases despite first-line bisphosphonate therapy.
abstract: OBJECTIVE
  This study evaluated whether additional palliative benefits could be derived from the second-line use of the more potent bisphosphonate zoledronic acid in metastatic breast cancer patients with either progressive bone metastases or skeletal-related events (SRE), despite first-line therapy with either pamidronate or clodronate.
  
  
  METHODS
  This prospective study evaluated the impact of second-line zoledronic acid on pain, quality of life, and markers of bone turnover (for example, urinary N-telopeptide [NTX]). Patients received monthly zoledronic acid (4 mg) for 3 months. Study evaluations were made weekly during the first month and again at week 8. No changes in chemotherapy or endocrine therapy were allowed in the month before or after commencing study treatment.
  
  
  RESULTS
  Thirty-one women completed this study. By week 8, patients had experienced significant improvements in pain control (P < .001). There was a downward trend in urinary NTX levels over the same time period (P = .008). Overall, there was a trend towards a positive correlation between improvement in pain control and reduction in week one urinary NTX relative to baseline (Spearman's rho r = 0.27; P = .15).
  
  
  CONCLUSIONS
  This is the first study to demonstrate that patients with either progressive bone metastases or SREs while on clodronate or pamidronate can have relevant palliative benefits with a switch to the more potent bisphosphonate zoledronic acid. This is reflected by significant improvements in pain control and bone turnover markers. If confirmed in randomized trials, these findings have major implications to the use of bisphosphonates in both the metastatic and adjuvant settings.
authors.affiliation: Division of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada. Mark.Clemons@uhn.on.ca
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Clemons
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.forename: Wei S
authors.initials: WS
authors.lastname: Ooi
authors.forename: Geetha
authors.initials: G
authors.lastname: Yogendran
authors.forename: Tatjana
authors.initials: T
authors.lastname: Sukovic
authors.forename: Betty Y L
authors.initials: BY
authors.lastname: Wong
authors.forename: Sunil
authors.initials: S
authors.lastname: Verma
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Maureen
authors.initials: M
authors.lastname: Trudeau
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004002:Clodronic Acid / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010166:Palliative Care; D000077268:Pamidronate; D011446:Prospective Studies; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid; D000077268:Pamidronate