Neoadjuvant Therapy With Docetaxel and Ketoconazole in Patients With High-Risk Prostate Cancer: A Pilot Study

Inclusion Criteria: * Patients must have histologically proven adenocarcinoma of the prostate. * Patients must meet at least one of the following high risk criteria: * PSA \> 20 * Gleason score 8 or greater * Presence of pathological Gleason grade 4 or higher as the majority sum on biopsy core * Greater than 50% of cores at time of biopsy positive for cancer * Clinical Stage T3 Disease * Patients must have PS of 0-1(ECOG) and medically deemed a surgical candidate for radical prostatectomy. * Age \> or = to 18. * Patients with a pre-existing peripheral neuropathy of equal to or greater than grade two are ineligible. * Serum Creatinine must be \< or equal to 2.0mg/dl. * Patients must currently not receiving any drug which is metabolized by cytochrome P450-3A4 including the statins, cyclosporin, terfenadine and erythromycin. * Prior to receiving any dose of docetaxel, patients should have absolute neutrophil counts \> 1,500, hemoglobin \> 8.0 g/dl and platelet counts \> 100,000/mm3. * Patients with bilirubin elevated above institutional upper limit of normal (ULN)must be excluded. Transaminases (SGOT and/or SGPT) may be up to 5.0 x institutional upper limit of normal (ULN) if alkaline phosphatase is \< ULN, or alkaline phosphatase may be up to 5 x ULN if transaminases are \< ULN. However, patients who have both transaminase elevation \> 1.5 x ULN and alkaline phosphatase \> 2.5 x ULN are not eligible for this study (due to decrease clearance of docetaxel and increased risk of toxicity). * Patients receiving concurrent warfarin are eligible but require monitoring of protime on a weekly basis. * Patients with clinical stage T4 disease are not eligible. * Patients must not had have received prior treatment with surgery, radiation or hormone deprivation. * Patients with other primary malignancies previously treated with chemotherapeutic agents are not eligible. * Patients must not have had a history of peptic ulcer disease requiring treatment with surgery or endoscleral. * Patients requiring corticosteroids for other systemic diseases are not eligible. * Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 are not eligible. * All patients must sign informed consent. * Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.