Calcitriol and Zoledronate in Treating Patients With Progressive Prostate Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of calcitriol administered with zoledronate in patients with progressive prostate cancer.
• Assess the effects of this regimen on calcium homeostasis and bone turnover in this patient population.
• Assess changes in PSA in patients treated with this regimen.
• Determine other antitumor effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study of calcitriol.

Patients receive oral calcitriol weekly for 3 consecutive days and zoledronate IV monthly. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of calcitriol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed prior localized adenocarcinoma of the prostate that has undergone definitive radiation or surgery and demonstrates progression biochemically with all of the following:

• Baseline PSA at least 4 ng/mL
• At least a 50% increase in PSA over at least 3 determinations taken at more than 2 week intervals
• No radiographically evident disease
• Neoadjuvant hormonal therapy prior to radical prostatectomy or radiotherapy allowed
• Treatment in an intermittent approach allowed if off therapy for at least 12 weeks OR
• Histologically confirmed androgen-independent adenocarcinoma of the prostate with all of the following:

• Progression on primary hormonal treatment (e.g., orchiectomy, estrogen therapy, gonadotropin-releasing hormone analog with or without an antiandrogen) with either new osseous lesions in bone, a greater than 25% increase in bidimensionally measurable tumor mass, or rising PSA values (rising PSA on any 3 determinations taken at at least weekly intervals, to greater than 50% above baseline PSA) despite castrate levels of testosterone (no greater than 30 ng/mL)
• If receiving antiandrogen as part of primary hormonal therapy, must meet criteria above for progression after discontinuation of antiandrogen
• No change in hormonal therapy (including prednisone or dexamethasone) within the past 2 weeks
• If no prior surgical orchiectomy, must continue on medical therapies to maintain castrate levels of testosterone
• Prior chemotherapy, palliative radiotherapy, or radioisotope treatment allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL OR
• SGOT less than 3 times upper limit of normal

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min
• No history of nephrolithiasis
• Must have 2 functioning kidneys

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Pulmonary:

• No severe debilitating pulmonary disease

Metabolic:

• No pre-existing endocrine or metabolic disorders that impact calcium regulatory axis including hypercalcemia (ionized serum calcium greater than 5.3 mg/dL or total calcium greater than 10.5 mg/dL) or hypercalciuria (greater than 300 mg urinary calcium/24 hours)

Other:

• No active secondary malignancy except nonmelanoma skin cancer
• Must maintain low calcium diet (less than 800 mg calcium daily)
• No uncontrolled serious active infection
• No history of malabsorption disorders
• No history of inflammatory bowel disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• Recovered from prior endocrine therapy

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy to sole measurable lesion

Surgery:

• See Disease Characteristics
• Recovered from prior surgery
• No concurrent surgery to sole measurable lesion

Other:

• No other concurrent cholecalciferol