A Randomized Double-Blind Placebo Controlled Phase III Trial Evaluating Zoledronate Plus Standard Therapy Versus Placebo Plus Standard Therapy in Patients With Recurrent Carcinoma of the Prostate Who Are Asymptomatic With Castrate Levels of Testosterone and Have Rising PSA Levels Without Radiologically-Evident Metastatic Disease

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven asymptomatic recurrent prostate cancer
Prior local treatment status Curatively treated OR Locally advanced disease noncuratively
treated with LHRH agonist therapy Currently receiving 1 line of hormonal therapy (with
LHRH agonists or surgical castration) and failing treatment with rising PSA only Patients
who received LHRH agonists instead of surgical castration continue to receive LHRH agonist
during study Biochemical progression documented by 3 consecutively rising PSA
measurements, each at least 2 weeks apart, with the last measurement being 50% or greater
than the nadir PSA achieved after the last therapeutic maneuver (first line hormonal
therapy as noted above) PSA (50% increased values) greater than 4 ng/mL for patients with
intact prostates and greater than 0.8 ng/mL for post-prostatectomy patients Rising PSA for
less than 10 months Castrate levels of testosterone (less than 30 ng/dL) No bone or
visceral metastases by bone scan and CT scan of abdomen and pelvis (except localized
abnormalities and pelvic lymph node and soft tissue disease) No CNS or leptomeningeal
involvement

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 90-100% Life
expectancy: Greater than 6 months Hematopoietic: WBC at least 3,000/mm3 Absolute
neutrophil count at least 1,500/mm3 Hemoglobin at least 8.0 g/dL Platelet count at least
75,000/mm3 Hepatic: Liver function tests no greater than 2.5 times upper limit of normal
(ULN) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart
Association class III or IV heart disease with uncontrolled and/or unstable cardiac or
coronary artery disease Other: No other malignancy within the past 5 years that would
confound the etiology of metastatic disease except curatively treated nonmelanomatous skin
cancer No other nonmalignant disease that would confound evaluation or preclude compliance
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic biologic anticancer therapy
Chemotherapy: No prior chemotherapy Concurrent chemotherapy such as estramustine
containing regimens or mitoxantrone allowed at the discretion of the protocol investigator
Endocrine therapy: See Disease Characteristics No prior systemic hormonal anticancer
therapy except LHRH antagonists and/or nonsteroidal antiandrogens (e.g., flutamide,
bicalutamide, or nilutamide) Concurrent aminoglutethimide, prednisone, or
diethylstilbestrol or other estrogens allowed at the discretion of the protocol
investigator Radiotherapy: At least 6 weeks since prior palliative radiotherapy Surgery:
See Disease Characteristics Other: No other prior systemic anticancer therapy At least 4
weeks since other prior investigational drugs No other concurrent bisphosphonate agent