ZOMETA® (Zoledronic Acid) for Prevention of Bone Metastases

Inclusion Criteria:

• Signed informed consent

• Age > 18 years

• Histologically confirmed diagnosis of carcinoma of the prostate

• ECOG performance status of 0, 1, or 2

• No radiological evident bone metastasis (negative bone scan or verification ofsuspected foci as benign lesions by additional radiological examination)

• T3-4 AND highest pre-study PSA >20 ng/ml AND Gleason score = 8 (or Gleason grade = 4)

• Patients with prior prostatectomy or prior local radiotherapy are eligible for thisstudy

• Patients are destined to receive medical (LHRH analogue) or surgical (orchiectomy)castration and Zometa® treatment will start not later than 6 weeks after surgery

• Patients should be fully recovered from prior interventions where applicable

Exclusion Criteria:

• Patients with a serum creatinine determination >265 µmol/L (3.0 mg/dL)

• Patients that received prior medical (LHRH analogue) castration

• Current (or previous) evidence of metastatic disease to the bone

• History of any other neoplasm within the past five years except for nonmelanomatousskin cancer.

• Previous hormonal therapy with LHRH agonists or other forms of hormonal ablation

• WBC<3.0x109, ANC < 1500/mm3, Hgb<8.0 g/dL, platelets < 75 x 109/L

• Liver function tests >2.5 ULN

• Prior treatment with Zometa® (zoledronic acid) or other bisphosphonates

• Treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to thedate of randomization (Visit 2)

• Use of other investigational drugs (drugs not marketed for any indication) within 30days prior to the date of randomization (Visit 2)

• Patients with evidence in the six months prior to randomization of severecardiovascular disease (defined as uncontrolled congestive heart failure),hypertension refractory to treatment, or symptomatic coronary artery diseaseuncontrolled by treatment

• History of noncompliance to medical regimens and patients who are consideredpotentially unreliable or incapable of giving informed consent as judged by theinvestigator.