Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer

A Randomized, Placebo Controlled Trial Of Zoledronic Acid For The Prevention Of Bone Loss In Premenopausal Women With Early Stage Breast Cancer

RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer.

OBJECTIVES:

• Compare the changes in bone mineral density (BMD) and bone turnover that occur in premenopausal women with resected early stage breast cancer during and after 6 months of adjuvant chemotherapy.
• Determine the factors that predict bone loss during chemotherapy, particularly induction of amenorrhea, type of chemotherapeutic regimen, glucocorticoid exposure, and baseline BMD, in these patients.
• Determine whether zoledronate prevents bone loss in these patients when given during and after adjuvant chemotherapy.
• Determine the effect of zoledronate on markers of bone turnover in these patients during and after adjuvant chemotherapy.
• Determine whether the effect on markers of bone turnover predicts response to zoledronate in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative), progesterone receptor status (positive vs negative), and adjuvant chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes on day 1.
• Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, treatment repeats every 3 months for up to 4 courses in the absence of disease progression. Patients also receive calcium and cholecalciferol (vitamin D) supplements daily.

Quality of life is assessed at baseline and at 6 and 12 months.

Patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of localized breast cancer

  • Stage I or II (T1-3, N0-2, M0)

• Planned adjuvant chemotherapy (after surgery) of at least 6 months in duration

• Hormone receptor status:

  • Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age

• 18 to 50

Sex

• Female

Menopausal status

• Premenopausal or perimenopausal

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine less than 2 mg/dL

Other

• No T score of less than 2.0 on bone mineral density (BMD)
• No fragility fracture
• No lumbar spine anatomy that would preclude accurate BMD measurement of a minimum of 3 lumbar vertebrae
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 1 month since prior calcitonin
• At least 12 months since prior bisphosphonates given for more than 1 month duration
• No concurrent fluoride therapy (10 mg/day or more)
• No concurrent enrollment in another experimental drug study