ZANTE: Zometa and Taxotere in Hormone Refractory Prostate Cancer

Docetaxel has been used alone and in combination with other anti-cancer therapies in the treatment of hormone refractory metastatic prostate cancer. Zoledronic acid has been used in the treatment of bone metastasis from prostate cancer. This is a study of the combination of these two agents. The Zante study will test a dose escalation of docetaxel in association with a predetermined dose of zoledronic acid (2 mg), given every 14 days for a minimum of 6 and maximum of 12 cycles.

Sequence A: Docetaxel on day 1 and zoledronic acid on day 2

Sequence B: Zoledronic acid on day 1 and docetaxel on day 2

Patients are enrolled sequentially in cohorts of 3 for each dose level, and a maximum of 36 patients will be enrolled.

Inclusion criteria

• Written informed consent
• Hormone refractory prostate cancer
• Stage IV disease with bone metastasis
• No immunotherapy, hormonal therapy or radiotherapy within the previous month
• Performance status < or = 2 (ECOG)
• Serum creatinine < 1.5 mg/100ml
• Serum bilirubin < or = 1.25 x UNL (upper normal limit) (or < or = 1.5 x UNL in the presence of hepatic metastases); SGOT e SGPT < or = 1.5 x UNL (or < or = 2.5 x UNL in presence of hepatic metastases)
• Left ventricular ejection fraction > or = 50% (measured by cardiac ultrasound or MUGA scan)
• Neutrophils > 1500/mm3; platelets >100000/mm3; hemoglobin >10 g/100 ml· Life expectancy of at least 3 months

Exclusion criteria

• Previous malignancies with the exception of radically treated epithelioma
• Previous chemotherapy
• Comorbidities that would, in the Investigator's opinion, contraindicate the use of the drugs in the study
• Uncontrolled Diabetes
• Severe cardiac arrhythmias, severe uncontrolled congestive heart failure, severe ischemic cardiac disease or myocardial infarction within the previous 6 months
• severe infection
• cerebral metastasis
• Pre-existing motor or sensory neurotoxicity > or = grade 2 according to CTC (Common Toxicity Criteria).