The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial

Oncology. 2011;81(5-6):298-305. doi: 10.1159/000334456. Epub 2011 Dec 8.

Abstract

Objective: This study reports the efficacy and safety of zoledronic acid (ZOL) in preventing bone loss in postmenopausal patients receiving an aromatase inhibitor (AI) following tamoxifen.

Methods: Postmenopausal patients with stage I-III hormone receptor-positive breast cancer who received tamoxifen for 2.5-3 years were randomized to receive letrozole (2.5 mg/day) with (n = 47) or without (n = 43) ZOL (4 mg i.v. every 6 months) for 2 years. The primary endpoint was percent change from baseline in lumbar spine (LS) bone mineral density (BMD) up to 60 months.

Results: Ninety patients (86 evaluable) with a median age of 59 years (42.9-83.6), 50/86 of whom had previously been treated with chemotherapy, were followed for a median time of 41.4 months. While the control group showed a significant decrease in LS T-score (p = 0.0005), the ZOL group presented an increase over time (p = 0.0143). Change over time in LS T-score was significantly different between groups, favoring ZOL (p < 0.0001 at 24 and 48 months). No fractures, renal dysfunction or osteonecrosis of the jaw were reported. The toxicity profile was similar to those previously reported for each drug.

Conclusion: The addition of ZOL to letrozole was safe and efficacious in maintaining LS BMD in postmenopausal patients with hormone receptor-positive breast cancer and who were receiving letrozole following 2.5-3 years of tamoxifen.

Trial registration: ClinicalTrials.gov NCT00376740.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Aromatase Inhibitors / therapeutic use
  • Bone Density / drug effects
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Drug Therapy, Combination / methods
  • Female
  • Follow-Up Studies
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Letrozole
  • Middle Aged
  • Neoplasm Staging / methods
  • Nitriles / therapeutic use*
  • Osteoporosis, Postmenopausal / prevention & control*
  • Prospective Studies
  • Tamoxifen / therapeutic use*
  • Triazoles / therapeutic use*
  • Zoledronic Acid

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Zoledronic Acid
  • Letrozole

Associated data

  • ClinicalTrials.gov/NCT00376740