Phase 3 Study of the Effect of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving the Aromatase Inhibitor, Letrozole, in the Adjuvant Setting
Letrozole is an aromatase inhibitor used in the treatment of hormone receptor positive
metastatic breast cancer in postmenopausal women.It has more recently been approved for use
in many countries as adjuvant therapy for early breast cancer; and is often used in an
adjuvant regimen following 2-3 years of tamoxifen treatment or as an extended adjuvant
therapy after up to 5 years of tamoxifen. Letrozole inhibits the conversion of androgens to
estrogens in vitro and in vivo. Plasma levels of estradiol and related estrogen compounds in
postmenopausal patients receiving letrozole are suppressed up to 95% from baseline and are
often undetectable.The estrogen deprivation in women receiving letrozole may cause increased
bone resorption and bone loss.Studies comparing tamoxifen and aromatase inhibitors, in
adjuvant therapy have shown an increase fracture rate, and decreased bone mineral density in
patients receiving aromatase inhibitors. Zoledronic acid is an intravenously administered
bisphosphonate that inhibits osteoclastic bone resorption. Intravenous bisphosphonates are
effective in reducing the rate of skeletal complications, including fractures, in patients
with metastatic breast cancer and other tumors when given every few weeks. Small clinical
trials have given some evidence that osteoporosis can be effectively treated by one or two
doses of intravenous zoledronic acid per year. This study will determine the effect of
giving zoledronic acid every 6 months on the bone mineral density of patients receiving
letrozole as adjuvant therapy for early breast cancer after having received adjuvant
tamoxifen for at least 2.5 years. Patients will be randomized to receive zoledronic acid
either at the start of letrozole therapy or when bone mineral density T score drops below -
2 standard deviation or at the occurrence of a non-trauma related fracture.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
bone mineral density
Tamar Safra, M.D.
Study Chair
Tel-Aviv Sourasky Medical Center
Israel: Ministry of Health
sor440006ctil
NCT00376740
September 2005
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