Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer
RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss.
PURPOSE: This randomized phase III trial is studying two forms of calcium with or without risedronate to compare how well they work in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, stage IIIA, or stage IIIB breast cancer.
Dietary Supplement: calcium carbonate
Dietary Supplement: cholecalciferol
Drug: risedronate sodium
|Study Design:||Allocation: Randomized
Primary Purpose: Supportive Care
|Official Title:||A Phase III Randomized, Placebo-Controlled, Double-Blind Trial Of Risedronate (Actonel) For Prevention Of Bone Loss In Premenopausal Women Undergoing Chemotherapy For Primary Breast Carcinoma|
- Average intra-patient change in lumbar spine (L2-L4, PA) bone mineral density (BMD) from baseline to one year after study entry
- Average intra-patient change in femoral neck and total hip BMD from baseline to one year after study entry
- Incidence of osteopenia in the risedronate vs placebo groups at one year after study entry
- Incidence of osteoporosis in the risedronate vs placebo groups at one year after study entry
- Incidence of a 5% difference in intra-patient BMD scores at baseline
- Serum and urine N-telopeptide and serum alkaline phosphatase at baseline and 6 months
- Frequency and severity of toxicity as measured by NCI CTC version 2.0
- Menopausal symptoms as measured by the Greene Climacteric Scale (GCS) at baseline, monthly during chemotherapy, at 6 months, 1 year, and 2 years after study entry
- Association of baseline serum estradiol levels with permanent cessation of menses
- Relationship between the subscales of the GCS (psychological, vasomotor, somatic and sexual) with type of chemotherapy, duration of chemotherapy, and menstrual cycle changes
|Study Start Date:||March 2003|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
- Compare the effectiveness of risedronate vs placebo in the prevention of bone loss in premenopausal women undergoing adjuvant or neoadjuvant chemotherapy for primary breast cancer.
- Compare the degree of bone loss over 1 year in these women according to menopausal status after 1 year of therapy.
- Determine the relationship of current climacteric symptoms, menstrual and reproductive history, and chemotherapy regimen with ovarian failure (permanent cessation of menses) in these women.
- Determine the relationship of baseline serum estradiol levels with ovarian failure in these women.
OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to planned tamoxifen therapy (yes vs no vs undecided), planned taxane therapy (yes vs no vs undecided), time from last menses (1-3 months vs longer than 3 months to 6 months), and age (under 40 vs 40 to 49 vs 50 and over). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral calcium and oral cholecalciferol daily and oral risedronate once weekly.
- Arm II: Patients receive calcium and cholecalciferol as in arm I and oral placebo once weekly.
In both arms, treatment begins during the first month of chemotherapy and continues for 1 year in the absence of unacceptable toxicity.
Questionnaires about cessation of menses, ovarian failure, and menopausal symptoms are completed at baseline, monthly during chemotherapy, at 6 months, and then at 1 and 2 years.
Patients are followed for 1 year.
PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study within 11 months.