zoledronate in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy

Conditions: Osteoporosis; Prostate Cancer

Summary: rationale: zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. it is not yet known whether zoledronate is more effective than calcium and vitamin d alone in preventing osteoporosis and bone fractures in patients with prostate cancer. purpose: this randomized phase iii trial is studying zoledronate to see how well it works compared to calcium and vitamin d alone in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy.

objectives: primary * compare the potential benefit of bisphosphonate therapy comprising zoledronate plus vitamin d and calcium supplement vs standard therapy with vitamin d and calcium supplement in the prevention of osteoporosis and associated bone fractures in patients with locally advanced nonmetastatic adenocarcinoma of the prostate undergoing radiotherapy and luteinizing hormone-releasing hormone (lhrh) agonist therapy. secondary * evaluate the potential benefit of these regimens on quality of life in these patients. * evaluate the potential benefit in bone mineral density over a period of 3 years for patients treated with these regimens. outline: this is randomized multicenter study. patients are stratified according to t score of the hip by dual x-ray absorptiometry (dxa) scan (\ -2.5 vs ≥ - 1.0) and planned duration of luteinizing hormone-releasing hormone (lhrh) agonist therapy (1-2½ years vs \> 2½ years). patients are randomized to 1 of 2 treatment arms. quality of life is assessed at baseline and every 6 months during treatment.

Eligibility criteria:
eligibility criteria: * pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 12 months of registration; * any one of the following clinical stages: * t3 disease, any n stage, m0 with any gleason score and any prostate-specific antigen (psa); \< t3 stage, any n stage, m0 with gleason's score ≥ 8 and any psa; \< t3 stage, any n stage, m0 with gleason's score 7 and psa ≥ 15 nanograms/ml; \< t3 stage, any n stage, m0 with gleason score \< 7 and psa ≥ 20 nanograms/ml. * a negative bone scan for metastatic disease; * it is mandatory that the treating physician determine the planned duration of lhrh therapy prior to the site registering the patient (minimum 1 year of therapy); if patient is receiving pre-treatment lhrh therapy, it must have begun ≤ 6 months prior to registration. if pelvic radiation therapy (rt) has started, it must have begun ≤ 8 weeks prior to registration; * appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup to be done within 16 weeks prior to registration: * history/physical examination; * dental evaluation, including history of dental surgery (e.g., extraction or implant); * bone scan; * t and l spine films; * dxa scan: to be eligible the patient must have a scan on lunar, hologic, or norland equipment only and the t scores in both the l spine and total hip must be \> negative 2.5; * zubrod performance status 0-1 within 16 weeks prior to registration; (8/16/07) * age ≥ 18; * serum creatinine within 4 weeks prior to registration (8/16/07) * corrected serum calcium ≥ 8.4 and ≤ 10.6 mg/dl within 8 weeks prior to registration; note: for patients with an albumin of 4.0, corrected calcium=measured calcium. the formula for corrected calcium if serum albumin value is above or below 4.0 is as follows: corrected calcium (mg/dl) = (4 - \[patient's albumin (g/dl)\] x 0.8) + patient's measured calcium (mg/dl) * patients who are sexually active must be willing/able to use medically acceptable forms of contraception, as the treatment involved in this study may be significantly teratogenic. * patient agrees to refrain from using all products listed in section 9.2, "non-permitted supportive therapy"; * post-prostatectomy patients are eligible. * patient must sign study specific informed consent prior to study entry. ineligibility criteria: * prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; e.g., carcinoma in situ of the breast or oral cavity are permissible; * patients with baseline t scores of ≤ -2.5 are excluded. * patients with baseline calculated creatinine clearance \< 30 ml/min (estimated by cockcroft-gault formula below) are excluded. creatinine clearance male = \[(140 - age) x (wt in kg)\] / \[(serum creatinine) x (72)\] * prior bisphosphonate therapy; * prior pelvic radiation (other than for current prostate cancer) or prior systemic radiotherapeutic agents, such as strontium or samarium; * patients receiving systemic chemotherapy, steroids, growth hormones, or calcitonin; * patients with a history of paget's disease or with uncontrolled thyroid or parathyroid dysfunction or with other diseases that influence bone metabolism; * known hypersensitivity to zoledronic acid or other bisphosphonates; * active dental problems at study entry, including infection of the teeth or jawbone; dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw, exposed bone in the mouth, or slow healing after dental procedures; * recent or planned

Keywords: osteoporosis adenocarcinoma of the prostate stage iib prostate cancer stage iia prostate cancer stage iii prostate cancer stage iv prostate cancer