Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer

OBJECTIVES:

• Compare the change in bone mineral density in patients with prostate cancer who are receiving androgen-ablation therapy treated with calcium and cholecalciferol with or without conjugated estrogens and with or without risedronate.
• Compare the toxicity of these regimens in these patients.
• Compare the changes in bone markers in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare hot flashes in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to duration of therapy with luteinizing hormone-releasing hormone agonists (no more than 30 days vs 31 to 150 days vs 151 to 365 days vs more than 365 days). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily.
• Arm II: Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily.
• Arm III: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily.
• Arm IV: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily.

Treatment in all arms continues for 2 years.

Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years.

Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years.

PROJECTED ACCRUAL: A total of 282 patients (70 per treatment arm) will be accrued for this study within 14 months.

DISEASE CHARACTERISTICS:

• History of prostate cancer

• No evidence of metastatic bony disease* NOTE: *Elevated prostate-specific antigen (PSA) allowed
• Meets one of the following criteria:

• Currently on treatment with androgen-ablation therapy in the adjuvant setting
• Rising PSA without other evidence of recurrent disease with planned treatment for at least 6 months
• No known osteoporosis or prior osteoporotic fracture

• Osteoporosis defined as bone density at the hip or spine of more than 2.5 standard deviations below the mean for young men

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• SGOT or SGPT no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase normal OR no greater than 1.5 times ULN with a normal bone scan

Renal

• Creatinine no greater than 1.5 times ULN
• No prior symptomatic hypercalcemia or hypocalcemia

Cardiovascular

• No active heart disease
• No congestive heart failure under active treatment
• No myocardial infarction within the past 5 years
• No coronary artery disease (CAD) with recent myocardial infarction

• Patients with a remote history of CAD who are only on medical treatment (e.g., antilipid agents) are allowed
• No prior thrombosis (deep vein thrombosis, stroke, or pulmonary embolism) or other known hypercoagulable state other than cancer

Other

• Fertile patients must use effective contraception
• Triglycerides no greater than 250 mg/dL (treatment allowed)
• Able to complete questionnaire(s) by self or with assistance
• Able to swallow pills
• No prior hyperlipidemia (e.g., prior familial hyperlipidemia or fasting triglyceride greater than 250 mg/dL within the past 6 months)
• No sarcoidosis
• No parathyroid dysfunction
• No intolerance to bisphosphonates

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent systemic steroids

Radiotherapy

• No concurrent radiotherapy

Surgery

• More than 3 months since prior and no concurrent dental extraction, root canal, or dental implantation

Other

• No prior bisphosphonates
• More than 5 years since prior percutaneous transluminal coronary angioplasty