title: A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer.
abstract: Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3 months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12 weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61 years (range 37-87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81 %) with zoledronic acid and 18/29 (62 %) with pamidronate (p = 0.095). Mean decrease in sCTx (mean difference between groups = 50 ng/L, 95 % CI 18-84; p = 0.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Kuchuk
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Bouganim
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.|The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.|The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mazzarello
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.|The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Vandermeer
authors.affiliation: Statistical Consultant, 283 Danforth Ave, Suite 448, Toronto, ON, M4K 1N2, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Dranitsaris
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Dent
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Gertler
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Song
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Simos
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Cella
authors.affiliation: Division of Medical Oncology and Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada. mclemons@toh.on.ca.|The Ottawa Hospital Research Institute, Ottawa, ON, Canada. mclemons@toh.on.ca.|Division of Medical Oncology, The Ottawa Hospital Cancer Centre, 501 Smyth Road, Box 900, Ottawa, ON, K1H8L6, Canada. mclemons@toh.on.ca.
authors.forename: M
authors.initials: M
authors.lastname: Clemons
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010166:Palliative Care; D000077268:Pamidronate; D011788:Quality of Life; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate
keywords: Bisphosphonate; Bone metastasis; Breast cancer; Pamidronate; Zoledronic acid